Affinage

IL1B

Interleukin-1 beta · UniProt P01584

Round 2 corrected
Length
269 aa
Mass
30.7 kDa
Annotated
2026-04-28
130 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-1β is a master pro-inflammatory cytokine produced as a 269-amino-acid precursor (proIL-1β) that is proteolytically matured to a ~17 kDa secreted form by caspase-1 activated within inflammasome complexes composed of sensor proteins (NALP1, NALP3, or AIM2), the adaptor ASC, and caspase-1 (PMID:12191486, PMID:15030775, PMID:19158679). IL-1β signals through IL-1R to recruit MyD88, which assembles a helical Myddosome with IRAK4 and IRAK2, culminating in TRAF6-catalyzed K63-polyubiquitin chain synthesis and IKK/NF-κB activation (PMID:9430229, PMID:20485341, PMID:11057907). Transcription of IL1B is governed in myeloid cells by a constitutive PU.1–IRF8–NTP-Stat1 complex at the LILRE enhancer with LPS-induced IRF8 phosphorylation as the activating trigger, whereas in CD4 T cells a bivalent H3K4me3+/H3K27me3+ chromatin state permits PU.1-independent transcription; CpG methylation at the −299 promoter site serves as an additional epigenetic switch, and autophagy-dependent degradation of PELI3 and PKM2 limits IL-1β output post-transcriptionally (PMID:17386941, PMID:30300855, PMID:23417678, PMID:25483963, PMID:31500508). Downstream, IL-1β drives Cox-2/PGE2-mediated central pain sensitization, stabilizes HIF-1α to link inflammation to angiogenesis, polarizes TH17 cells, disrupts intestinal tight junctions via miR-200c-3p-mediated occludin degradation, and operates in an autocrine glucotoxic loop that promotes pancreatic β-cell apoptosis (PMID:11260714, PMID:12958148, PMID:22466287, PMID:32569770, PMID:12235117).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1984 High

    Cloning of human and murine IL-1β cDNAs established that IL1B encodes a precursor polypeptide whose carboxy-terminal ~153–156 residues constitute the biologically active mature cytokine, resolving the molecular identity and domain organization of IL-1β.

    Evidence cDNA cloning from monocyte/macrophage libraries, E. coli expression of truncation constructs, Xenopus oocyte translation, and bioassay

    PMID:2989698 PMID:6083565 PMID:6209582

    Open questions at the time
    • Mechanism of precursor cleavage unknown at this point
    • Signal-less secretion pathway uncharacterized
    • No structural information on mature IL-1β
  2. 1997 High

    Identification of MyD88 as the IL-1R-proximal adaptor that bridges receptor engagement to IRAK recruitment answered how IL-1β transduces signal from the plasma membrane to the NF-κB cascade.

    Evidence Co-immunoprecipitation, dominant-negative death domain constructs, NF-κB reporter assays showing IL-1-specific but not TNF-specific blockade

    PMID:9430229

    Open questions at the time
    • Stoichiometry and oligomeric state of the signaling complex unknown
    • How IRAK activates downstream kinases not yet resolved
  3. 2000 High

    Demonstration that TRAF6 activates IKK through Ubc13/Uev1A-catalyzed K63-linked polyubiquitin chains completed the biochemical link between IL-1R engagement and NF-κB activation, establishing a non-degradative ubiquitin signaling paradigm downstream of IL-1β.

    Evidence Biochemical reconstitution with purified proteins, mass spectrometry identification of Ubc13/Uev1A, in vitro IKK activation assay, dominant-negative blockade

    PMID:11057907

    Open questions at the time
    • K63-chain deubiquitinase regulation not identified
    • Exact chain attachment sites on TRAF6 substrates unresolved
  4. 2002 High

    Discovery of the inflammasome as a multiprotein complex (NALP1/ASC/caspase-1/caspase-5) that activates caspase-1 to process proIL-1β resolved the long-standing question of how the leaderless precursor is matured, establishing the two-signal model of IL-1β production.

    Evidence Cell-free reconstitution, immunodepletion of ASC abolishing processing, dominant-negative ASC in THP-1 cells

    PMID:12191486

    Open questions at the time
    • Upstream danger signals that trigger assembly unknown
    • Other NLR sensor proteins not yet identified
  5. 2002 High

    The finding that high glucose induces β-cells themselves to produce IL-1β in an autocrine loop that drives NF-κB activation, Fas upregulation, and apoptosis established a non-immune-cell source and pathogenic function of IL-1β in type 2 diabetes glucotoxicity.

    Evidence Human islet culture, ELISA, NF-κB reporter, TUNEL, IL-1Ra blockade, in vivo model

    PMID:12235117

    Open questions at the time
    • Mechanism of proIL-1β processing in β-cells (caspase-1-dependent or alternative) not defined
    • Whether IL-1Ra therapy rescues β-cell mass in vivo not fully resolved
  6. 2003 High

    IL-1β was shown to stabilize HIF-1α under normoxia through an NF-κB/COX-2/PGE2 pathway that antagonizes VHL-dependent degradation, providing a molecular link between inflammation, angiogenesis, and oncogenesis.

    Evidence Reporter assays, Western blot, COX-2 and NF-κB inhibitor epistasis, HIF-1α protein stability measurements

    PMID:12958148

    Open questions at the time
    • Precise post-translational modification on HIF-1α affected by PGE2 unknown
    • In vivo relevance to tumor angiogenesis not demonstrated
  7. 2004 High

    Identification of NALP3 as a second inflammasome sensor, with gain-of-function mutations in Muckle-Wells patients causing spontaneous IL-1β release, expanded the inflammasome concept and connected IL-1β to autoinflammatory disease.

    Evidence Co-immunoprecipitation of NALP3/ASC/Cardinal/caspase-1 complex, caspase-1 activity assay, patient macrophage studies

    PMID:15030775

    Open questions at the time
    • Molecular triggers for NALP3 activation not identified
    • How NALP3 mutations bypass the two-signal requirement unclear
  8. 2006 High

    Pannexin-1 hemichannels were identified as required for P2X7-triggered caspase-1 processing and IL-1β release, addressing how the second signal (extracellular ATP) mechanistically couples to inflammasome activation.

    Evidence Pannexin-1 siRNA knockdown abolishing both membrane pore formation and IL-1β secretion, electrophysiology, dye uptake assay

    PMID:17036048

    Open questions at the time
    • Whether pannexin-1 is universally required for all inflammasome activators or is P2X7-specific
    • Physical interaction between pannexin-1 and inflammasome components not shown
  9. 2007 High

    Characterization of the PU.1–IRF8–NTP-Stat1 trimolecular complex pre-bound at the LILRE enhancer, with LPS-induced IRF8 tyrosine phosphorylation as the activating switch, defined the myeloid-specific transcriptional mechanism governing IL1B induction.

    Evidence ChIP, EMSA with recombinant proteins, reporter assay, IRF8 Y211F dominant-negative mutagenesis

    PMID:17386941

    Open questions at the time
    • Kinase responsible for IRF8 Y211 phosphorylation not identified
    • Whether this enhancer mechanism operates in all myeloid subsets unknown
  10. 2009 High

    Multiple advances in 2009 refined IL-1β regulation: AIM2 was identified as a cytoplasmic dsDNA sensor forming a third inflammasome platform for IL-1β processing; miR-155 was shown to dampen IL-1β output by targeting TAB2 in a negative feedback loop; and human monocytes were found to constitutively activate caspase-1 requiring only one signal for IL-1β release, unlike macrophages.

    Evidence AIM2: proteomic/genomic screen, HEK293 reconstitution, RNAi; miR-155: 3'UTR reporter validation, LNA silencing, cytokine ELISA; monocyte: NALP3/ASC siRNA, ATP measurement, caspase-1 activity

    PMID:19104081 PMID:19158679 PMID:19193853

    Open questions at the time
    • AIM2 ligand length and sequence requirements not defined
    • Mechanism of constitutive caspase-1 activation in monocytes unclear
    • miR-155 contribution relative to other post-transcriptional regulators not quantified
  11. 2010 High

    The crystal structure of the MyD88–IRAK4–IRAK2 Myddosome revealed a left-handed helical 6:4:4 death domain oligomer, explaining how IL-1R engagement nucleates IRAK kinase trans-phosphorylation and resolving the stoichiometric basis of signal amplification.

    Evidence X-ray crystallography, interface mutagenesis with functional signaling assays

    PMID:20485341

    Open questions at the time
    • How Myddosome disassembly is regulated not addressed
    • Whether other IRAKs substitute in specific cell types unclear
  12. 2012 High

    IL-1β was established as essential for human TH17 cell differentiation and functional polarization, counteracting IL-12 and suppressing IL-10 in both naive and memory TH17 cells, thereby extending IL-1β's role from innate immunity to adaptive immune programming.

    Evidence In vitro naive T-cell priming, in vivo IL-1β blockade, intracellular cytokine staining across antigen-specific and memory subsets

    PMID:22466287

    Open questions at the time
    • Transcription factors downstream of IL-1R in T cells mediating IL-10 suppression not identified
    • Whether IL-1β requirement is pathogen-specific beyond Candida not tested
  13. 2013 High

    CpG methylation at the −299 site was identified as the primary epigenetic switch controlling IL1B transcription, with demethylation correlating with high expression in human chondrocytes, adding a DNA methylation layer to the transcriptional regulation previously attributed to transcription factors alone.

    Evidence Bisulfite sequencing in situ, CpG-free reporter with site-directed methylation mutants, ChIP

    PMID:23417678

    Open questions at the time
    • Demethylase responsible for −299 CpG demethylation not identified
    • Whether this site is the dominant switch in other tissues unknown
  14. 2014 High

    Two discoveries in 2014 expanded IL-1β biology: caspase-1-dependent pyroptosis was identified as the principal CD4 T-cell death pathway during HIV-1 infection with concomitant IL-1β release linking depletion to chronic inflammation, and autophagy-dependent degradation of the E3 ligase PELI3 was shown to dampen Il1b mRNA expression.

    Evidence HIV: caspase-1 inhibitors in primary human lymphoid explants blocking both CD4 death and IL-1β release; PELI3: siRNA, autophagy inhibition, ubiquitination assay, K316R mutagenesis

    PMID:24356306 PMID:25483963

    Open questions at the time
    • Whether caspase-1 inhibition can reduce HIV-induced inflammation in vivo clinically unknown
    • PELI3 substrates relevant to Il1b transcription not identified
  15. 2018 High

    Discovery that CD4 T cells activate IL1B transcription from a bivalent H3K4me3+/H3K27me3+ chromatin state independently of PU.1 revealed a lymphoid-specific epigenetic regulatory mechanism fundamentally different from the myeloid PU.1–IRF8 pathway.

    Evidence ChIP for bivalent histone marks, qRT-PCR, Western blot, flow cytometry comparing CCR5+ vs CCR5− subsets

    PMID:30300855

    Open questions at the time
    • Transcription factor that replaces PU.1 in T cells not identified
    • Stimulus that resolves the bivalent state not defined
  16. 2020 High

    IL-1β was shown to disrupt intestinal tight junctions by upregulating miR-200c-3p, which degrades occludin mRNA, establishing a miRNA-mediated mechanism by which IL-1β increases epithelial barrier permeability.

    Evidence miRNA reporter assay, antagomiR rescue in vitro and in vivo intestinal perfusion, mutational mapping of miRNA-mRNA interaction site

    PMID:32569770

    Open questions at the time
    • Whether other tight junction proteins are co-regulated by the same miRNA not tested
    • Relevance to IBD barrier dysfunction in patients not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the kinase phosphorylating IRF8 at Y211 to trigger myeloid IL1B transcription, the transcription factor substituting for PU.1 in T-cell IL1B expression, the structural basis of NALP3 activation and the molecular triggers that distinguish sterile from microbial inflammasome assembly, and the relative contributions of multiple unconventional secretion routes for leaderless IL-1β in different physiological contexts.
  • IRF8 Y211 kinase identity unknown
  • T-cell-specific IL1B transcription factor unidentified
  • Structural mechanism of NLRP3 activation incompletely resolved
  • Quantitative comparison of unconventional secretion pathways lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 8
Localization
GO:0005576 extracellular region 6 GO:0005829 cytosol 3
Pathway
R-HSA-168256 Immune System 9 R-HSA-162582 Signal Transduction 5 R-HSA-9612973 Autophagy 3 R-HSA-5357801 Programmed Cell Death 2
Partners
AIM2CASP1IL1R1IRAK4MYD88NLRP3PYCARDTRAF6
Complex memberships
AIM2 inflammasomeMyddosomeNLRP1 inflammasomeNLRP3 inflammasome

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1984 IL1B was cloned from a human monocyte cDNA library and shown to encode a 269 amino acid precursor polypeptide (30,747 Mr); mRNA selected by hybridization to this cDNA was translated in vitro and injected into Xenopus oocytes, which secreted biologically active IL-1β, establishing that the precursor is subsequently processed to the ~15–20 kDa mature form. cDNA cloning, hybrid-selected translation in reticulocyte lysate, Xenopus oocyte expression, immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 6083565
1984 Murine IL-1 (ortholog of IL1B) was cloned and expressed in E. coli; biological activity was confined to the carboxy-terminal 156 amino acids of the 270 amino acid precursor, defining the minimal bioactive domain of the IL-1β precursor. cDNA cloning, E. coli expression of truncated constructs, bioassay Nature High 6209582
1985 Two distinct human IL-1 cDNAs (IL-1α and IL-1β) were isolated from a macrophage library; the primary translation products are 271 and 269 amino acids respectively, and expression of the carboxy-terminal 153 amino acids of IL-1β in E. coli produces IL-1 biological activity, confirming the precursor-to-mature processing model. cDNA library screening, E. coli expression, bioassay Nature High 2989698
1997 MyD88 is recruited to the IL-1 receptor complex upon IL-1 stimulation, physically bridges the receptor heterodimer to IRAK, and its ectopic expression or isolated death domain activates NF-κB; the C-terminus of MyD88 blocks IL-1-induced NF-κB but not TNF-induced NF-κB, placing MyD88 as the immediate IL-1R adapter that recruits IRAK. Co-immunoprecipitation, ectopic expression, dominant-negative constructs, NF-κB reporter assay Immunity High 9430229
2000 IL-1β-stimulated TRAF6 activates IKK (and thus NF-κB) through the heterodimeric ubiquitin-conjugating enzyme complex Ubc13/Uev1A, which catalyzes synthesis of K63-linked polyubiquitin chains; blockade of this chain synthesis (but not proteasome inhibition) prevents IKK activation downstream of IL-1R signaling. Protein purification, mass spectrometry, in vitro ubiquitination assay, IKK activation assay, dominant-negative expression Cell High 11057907
2000 IL1B promoter polymorphisms (especially the -511 TATA-box variant) that enhance IL-1β production are associated with risk of H. pylori-induced hypochlorhydria and gastric cancer; in vitro EMSA demonstrated that the -31 TATA-box polymorphism markedly alters DNA-protein interactions, providing a molecular mechanism by which the SNP affects transcription. Case-control genetics, EMSA (electrophoretic mobility shift assay) Nature Medium 10746728
2001 Peripheral inflammation induces widespread Cox-2 expression in spinal cord neurons, elevating cerebrospinal fluid PGE2; the critical inducer of central Cox-2 upregulation is IL-1β acting in the CNS, as intraspinal injection of an IL-1-converting enzyme inhibitor or a Cox-2 inhibitor reduced central PGE2 and mechanical hyperalgesia, placing IL-1β upstream of Cox-2-mediated central sensitization. In vivo rodent model, intraspinal drug injection, Cox-2 immunostaining, PGE2 measurement, behavioral pain testing Nature High 11260714
2002 The inflammasome — a multiprotein complex comprising caspase-1, caspase-5, Pycard/ASC, and NALP1 — was identified as the molecular platform that activates caspase-1 and processes proIL-1β to mature IL-1β; immunodepletion of Pycard in a cell-free system abolished proIL-1β processing, and dominant-negative Pycard blocked proIL-1β maturation in THP-1 cells after LPS stimulation. Cell-free reconstitution, immunodepletion, dominant-negative expression, caspase activity assay, IL-1β processing assay Molecular cell High 12191486
2002 High glucose concentrations induce β-cells themselves (not just immune cells) to produce and release IL-1β, which then activates NF-κB, upregulates Fas, and promotes β-cell apoptosis; the IL-1 receptor antagonist blocked these glucose-induced effects, establishing an autocrine glucotoxic IL-1β loop in human pancreatic islets. Human islet culture, ELISA, NF-κB reporter, Fas immunostaining, TUNEL apoptosis assay, IL-1Ra blockade, in vivo animal model The Journal of clinical investigation High 12235117
2003 IL-1β upregulates HIF-1α protein under normoxia via an NF-κB/COX-2/PGE2 pathway; the induction involves both new transcription and a post-transcriptional mechanism antagonizing VHL-dependent HIF-1α degradation (increased protein stability), leading to VEGF upregulation and linking inflammation to oncogenesis. Reporter assay, Western blot, NF-κB inhibition, COX-2 inhibitor treatment, PGE2 addition, HIF-1α stability assay FASEB journal High 12958148
2004 NALP3 (with NALP2) associates with ASC, the CARD-containing protein Cardinal, and caspase-1 to form an inflammasome with high proIL-1β-processing activity; macrophages from Muckle-Wells patients (carrying gain-of-function NALP3 mutations) spontaneously secrete active IL-1β, establishing that NALP3-dependent inflammasome activation drives IL-1β maturation. Co-immunoprecipitation, caspase-1 activity assay, IL-1β processing assay, patient macrophage studies Immunity High 15030775
2006 P2X7 receptor activation in macrophages leads to IL-1β release via pannexin-1 hemichannels; pannexin-1 mediates the large membrane pore responsible for dye uptake and is required for caspase-1 processing and mature IL-1β release, as siRNA knockdown of pannexin-1 abolished both pore formation and IL-1β secretion induced by P2X7 stimulation. Electrophysiology, dye uptake assay, siRNA knockdown, caspase-1 processing assay, IL-1β ELISA The EMBO journal High 17036048
2007 Non-tyrosine-phosphorylated (NTP)-Stat1 participates in a constitutive trimolecular complex with Spi-1/PU.1 and IRF8 pre-bound at the LPS/IL-1 response element (LILRE) of the IL1B promoter; LPS induces tyrosine phosphorylation of IRF8 (but not Stat1), which is required for IL1B transactivation. A Y211F IRF8 dominant-negative abrogated LPS-induced IL1B reporter activity, and ectopic NTP-Stat1 Y701F enhanced it. Chromatin immunoprecipitation, EMSA, reporter assay, site-directed mutagenesis, dominant-negative expression, in vitro DNA binding with recombinant proteins Molecular immunology High 17386941
2007 The IL1B -31 T/C SNP differentially regulates promoter activity: the T variant drives higher transcription than the C variant in lung epithelial A549 cells. EMSA revealed a unique protein complex on the C allele not present on the T allele; supershift identified C/EBPβ and TBP as components of this complex, explaining allele-specific differences in IL1B expression. Luciferase reporter assay, EMSA, supershift assay Cytokine Medium 17587593
2008 Intracellular HMGB1 physically interacts with the Ets transcription factor PU.1 (Spi-1) and co-operates with it to transactivate the IL1B promoter. GST pulldown and co-immunoprecipitation demonstrated direct HMGB1-PU.1 interaction; EMSA showed a ternary complex of PU.1, HMGB1, and the PU.1-binding element in the IL1B promoter. Deletion of the PU.1 winged helix-turn-helix domain abolished the interaction. GST pulldown, co-immunoprecipitation, EMSA, reporter assay, domain deletion mutagenesis European journal of haematology High 18173740
2009 AIM2, identified by crossing a proteomic screen for DNA-binding proteins with interferon-stimulated gene transcripts, senses cytoplasmic dsDNA, recruits the inflammasome adapter ASC, and is necessary and sufficient for IL-1β maturation: AIM2 knockdown impaired DNA-induced IL-1β processing in THP-1 cells, and reconstitution of HEK293 cells with AIM2, ASC, caspase-1, and proIL-1β was sufficient for inflammasome activation. Proteomic/genomic screen, Co-immunoprecipitation, RNAi knockdown, HEK293 reconstitution assay, IL-1β processing assay Nature immunology High 19158679
2009 MiR-155 is upregulated by LPS in human monocyte-derived dendritic cells and directly targets TAB2, a signal transduction component of the TLR/IL-1 pathway, forming a negative feedback loop that dampens inflammatory cytokine (including IL-1β) production in response to microbial stimuli. LNA silencing, microarray, luciferase 3'UTR reporter (target validation), cytokine ELISA Proceedings of the National Academy of Sciences of the United States of America High 19193853
2009 Human blood monocytes release processed, mature IL-1β after a single TLR2 or TLR4 stimulation due to constitutively activated caspase-1, driven by constitutive NALP3 and ASC activity and autocrine ATP release. In contrast, macrophages require a second ATP stimulus (two-signal requirement) for IL-1β processing, demonstrating cell-type-specific uncoupling of caspase-1 activation from PRR signaling. IL-1β ELISA, caspase-1 activity assay, NALP3/ASC siRNA knockdown, ATP measurement, pharmacological inhibitors Blood High 19104081
2010 The crystal structure of the MyD88-IRAK4-IRAK2 death domain complex revealed a left-handed helical oligomer (Myddosome) comprising 6 MyD88, 4 IRAK4, and 4 IRAK2 DDs; this hierarchical assembly brings IRAK kinase domains into proximity for trans-phosphorylation and activation. Key interface mutations predicted from the structure abrogated signaling, explaining how IL-1R/TLR engagement triggers the IL-1β-driven NF-κB cascade. X-ray crystallography, site-directed mutagenesis, functional signaling assays Nature High 20485341
2011 IL-1β secretion does not follow the conventional ER-Golgi secretory route; multiple mechanisms contribute on a continuum depending on stimulus strength, including caspase-1-dependent and caspase-1-independent pathways, and extracellular vesicle release, as reviewed from diverse experimental systems. Review and synthesis of reconstitution, pharmacological, and cell-biological studies Cytokine & growth factor reviews Medium 22019906
2012 IL-1β is essential for differentiation of Candida albicans-specific human TH17 cells that co-produce IL-17 and IFN-γ; IL-1β counteracts IL-12-mediated inhibition during priming and suppresses IL-10 production in both differentiating and memory TH17 cells. In vivo blockade of IL-1β increased IL-10 production by memory TH17 cells, establishing IL-1β as a directional regulator of TH17 functional polarization. In vitro naive T-cell priming, cytokine neutralization/blockade, in vivo IL-1β blockade, intracellular cytokine staining, memory T-cell restimulation Nature High 22466287
2013 CpG methylation at the -299 bp site in the proximal IL1B promoter strongly suppresses transcriptional activity; in situ methylation analysis of human chondrocytes correlated demethylation of this site with high IL1B expression. Transfection of CpG-free luciferase reporters with site-directed CpG mutants confirmed that methylation of the -299 site is the primary epigenetic switch for IL1B transcription in chondrocytes, operating through a mechanism distinct from HIF-2α (which regulates the adjacent MMP13 promoter -110 CpG). In situ bisulfite methylation analysis, CpG-free luciferase reporter transfection with site-directed mutagenesis, chromatin immunoprecipitation The Journal of biological chemistry High 23417678
2014 Caspase-1-mediated pyroptosis, not caspase-3-mediated apoptosis, is the principal death pathway for CD4 T cells during HIV-1 infection in lymphoid tissue; pyroptotic CD4 T cells release IL-1β, linking the two signature events of HIV — CD4 depletion and chronic inflammation. Caspase-1 inhibitors blocked both CD4 T-cell death and IL-1β release. Primary human lymphoid tissue explants, caspase-1 and caspase-3 activity assays, caspase-1 inhibitor treatment, IL-1β ELISA, flow cytometry Nature High 24356306
2014 Autophagy-dependent degradation of PELI3 (Pellino3), an E3 ubiquitin ligase and TLR4-scaffold protein, attenuates Il1b mRNA expression in macrophages; PELI3 is ubiquitinated upon LPS stimulation, binds the autophagy receptor SQSTM1/p62, and colocalizes with LC3B and LAMP2. Mutation of PELI3 lysine-316 (K316R) reduced Torin2-dependent PELI3 degradation, identifying this residue as required for autophagic targeting. siRNA knockdown (Sqstm1, Atg7), pharmacological autophagy inhibition, proteasome inhibition, immunofluorescence co-localization, ubiquitination assay, site-directed mutagenesis (K316R), qRT-PCR of Il1b Autophagy High 25483963
2017 PTPN22 loss leads to enhanced NLRP3 phosphorylation, which promotes sequestration of phospho-NLRP3 into autophagosomes, thereby reducing NLRP3 inflammasome activation and IL-1β (IL1B) secretion. Inhibition of autophagy abrogated the inhibitory effect on NLRP3 activation seen in PTPN22-deficient cells, and phosphorylated (but not non-phosphorylated) NLRP3 was found in autophagosomes. Autophagy inhibition (pharmacological and genetic), NLRP3 phosphorylation analysis, autophagosome fractionation, IL-1β secretion assay Autophagy High 28786745
2018 In CD4 T cells, IL1B gene transcription occurs independently of Spi-1/PU.1 (which is required in monocytes) and proceeds from a bivalent H3K4me3+/H3K27me3+ chromatin state at the IL1B promoter; CD3/CD28 stimulation increases IL1B transcription and translation, and the CCR5+ effector memory subset expresses higher proIL-1β than CCR5- T cells, revealing a lymphoid-specific epigenetic regulatory mechanism. ChIP for H3K4me3/H3K27me3, qRT-PCR, Western blot, flow cytometry (cell subset comparison), ex vivo CD3/CD28 activation Cytokine High 30300855
2019 SQSTM1-dependent autophagic degradation of PKM2 (pyruvate kinase M2) inhibits production of mature IL-1β in macrophages; LIPUS (low-intensity pulsed ultrasound) upregulates autophagy and promotes SQSTM1-PKM2 complex formation. SQSTM1 knockdown reversed the LIPUS-induced decrease in PKM2 and restoration of mature IL-1β, placing PKM2 as a pro-IL-1β factor whose autophagic clearance limits inflammasome output. siRNA knockdown, co-immunoprecipitation (SQSTM1-PKM2 complex), Western blot (LC3, Beclin-1, PKM2), ELISA (IL-1β), transmission electron microscopy Autophagy High 31500508
2020 IL1B increases intestinal tight junction permeability by upregulating MIR200C-3p, which directly degrades occludin mRNA via its 3'UTR; 3D molecular modeling and mutational analyses identified the specific nucleotide bases of the occludin mRNA 3'UTR that interact with MIR200C-3p, and antagomiR-200C prevented IL1B-induced decrease in occludin and the increase in TJ permeability both in vitro and in vivo. miRNA reporter assay, immunoblot, qRT-PCR, transfection with miRNA vectors, antagomiR treatment, intestinal perfusion in vivo, 3D molecular modeling with mutational analysis Gastroenterology High 32569770
2009 The IL1B -31 polymorphism-driven differential expression of IL-1β modulates gastrin expression at the transcriptional level via NF-κB and HDACs; the -31T IL1B variant drives ~10-fold higher promoter activity than -31C, and IL1B (induced by -31T) represses gastrin promoter activity ~2-fold more than -31C-driven IL1B, with ~1.5-fold greater NF-κB activation. Promoter-reporter transfection, IL1B expression plasmids with allelic variants, NF-κB reporter assay, HDAC inhibitor experiments, gastrin ELISA The international journal of biochemistry & cell biology Medium 19166966

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Molecular cell 4956 12191486
2013 Activation and regulation of the inflammasomes. Nature reviews. Immunology 2367 23702978
2016 Mechanism and Regulation of NLRP3 Inflammasome Activation. Trends in biochemical sciences 2273 27669650
2009 Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomatic medicine 2179 19188531
2000 Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 1849 10746728
1985 Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature 1766 2989698
2000 Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 1526 11057907
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2004 NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 1452 15030775
2006 Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. The EMBO journal 1217 17036048
1984 Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proceedings of the National Academy of Sciences of the United States of America 1198 6083565
2003 Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 1167 12606524
2011 Understanding the mechanism of IL-1β secretion. Cytokine & growth factor reviews 1163 22019906
2001 Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 1000 11260714
1984 Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. Nature 978 6209582
2002 Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. The Journal of clinical investigation 969 12235117
2014 Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 909 24356306
1997 MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 889 9430229
2010 Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature 882 20485341
2009 An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nature immunology 857 19158679
2008 Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nature genetics 817 18583979
2012 Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. Nature 775 22466287
2003 Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology 719 12730860
2008 Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages. Blood 667 19104081
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2003 IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 589 12958148
2002 De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis and rheumatism 588 12483741
2009 MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 584 19193853
2002 The balance between IL-1 and IL-1Ra in disease. Cytokine & growth factor reviews 577 12220547
2002 Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. Journal of the National Cancer Institute 492 12441323
2020 IL1B Increases Intestinal Tight Junction Permeability by Up-regulation of MIR200C-3p, Which Degrades Occludin mRNA. Gastroenterology 193 32569770
2019 Endogenous Production of IL1B by Breast Cancer Cells Drives Metastasis and Colonization of the Bone Microenvironment. Clinical cancer research : an official journal of the American Association for Cancer Research 148 30670488
2018 The role of IL-1B in breast cancer bone metastasis. Endocrine-related cancer 148 29760166
2021 Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis. The Journal of experimental medicine 134 34279540
2009 DNA demethylation at specific CpG sites in the IL1B promoter in response to inflammatory cytokines in human articular chondrocytes. Arthritis and rheumatism 132 19877066
1999 IL1B gene polymorphisms influence the course and severity of inflammatory bowel disease. Immunogenetics 124 10380697
2013 Regulated transcription of human matrix metalloproteinase 13 (MMP13) and interleukin-1β (IL1B) genes in chondrocytes depends on methylation of specific proximal promoter CpG sites. The Journal of biological chemistry 119 23417678
2017 PTPN22 regulates NLRP3-mediated IL1B secretion in an autophagy-dependent manner. Autophagy 108 28786745
2019 SQSTM1-dependent autophagic degradation of PKM2 inhibits the production of mature IL1B/IL-1β and contributes to LIPUS-mediated anti-inflammatory effect. Autophagy 105 31500508
2004 Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. Genes and immunity 104 15190266
2006 Interleukin 1beta (IL1B) signaling is a critical component of radiation-induced skin fibrosis. Radiation research 85 16435917
1999 Interleukin-4 and interleukin-10 regulate IL1-beta induced mouse primary astrocyte activation: a comparative study. Glia 66 10088668
2004 IL1B and IL1RN polymorphic genes and Helicobacter pylori cagA strains decrease the risk of reflux esophagitis. Gastroenterology 61 15236174
2008 Association of -31T>C and -511 C>T polymorphisms in the interleukin 1 beta (IL1B) promoter in Korean keratoconus patients. Molecular vision 60 19043479
2014 Autophagy-dependent PELI3 degradation inhibits proinflammatory IL1B expression. Autophagy 59 25483963
2007 Differential binding of proteins to the IL1B -31 T/C polymorphism in lung epithelial cells. Cytokine 59 17587593
2016 Resveratrol Interferes with IL1-β-Induced Pro-Inflammatory Paracrine Interaction between Primary Chondrocytes and Macrophages. Nutrients 58 27187448
2002 T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region. Genes and immunity 57 11857060
2015 TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in the Mexican Population. PloS one 56 26657940
2010 Macrophage-derived LIF and IL1B regulate alpha(1,2)fucosyltransferase 2 (Fut2) expression in mouse uterine epithelial cells during early pregnancy. Biology of reproduction 52 20864644
2007 Association of CD14, IL1B, IL6, IL10 and TNFA functional gene polymorphisms with symptomatic dental abscesses. International endodontic journal 52 17511783
2021 IL-1B drives opposing responses in primary tumours and bone metastases; harnessing combination therapies to improve outcome in breast cancer. NPJ breast cancer 51 34290237
2016 Sucrose, But Not Glucose, Blocks IL1-β-Induced Inflammatory Response in Human Chondrocytes by Inducing Autophagy via AKT/mTOR Pathway. Journal of cellular biochemistry 51 27669541
2010 Association of IL1B -511C/-31T haplotype and Helicobacter pylori vacA genotypes with gastric ulcer and chronic gastritis. BMC gastroenterology 51 20979650
2007 Association of polymorphisms in the IL1B and IL2 genes with susceptibility and severity of systemic sclerosis. The Journal of rheumatology 51 17444587
2006 Interaction between IL1B gene promoter polymorphisms in determining susceptibility to Helicobacter pylori associated duodenal ulcer. Human mutation 50 16550552
2005 NOD2/CARD15 and TNFA, but not IL1B and IL1RN, are associated with Crohn's disease. Inflammatory bowel diseases 47 15803022
2013 Genetic variants in IL1A and IL1B contribute to the susceptibility to 2009 pandemic H1N1 influenza A virus. BMC immunology 46 23927441
2006 Analysis of IL1B, TAP1, TAP2 and IKBL polymorphisms on susceptibility to tuberculosis. Tissue antigens 46 16634865
2016 Effects of IL1B single nucleotide polymorphisms on depressive and anxiety symptoms are determined by severity and type of life stress. Brain, behavior, and immunity 45 26891860
2009 Association of IL-1B genetic polymorphisms with an increased risk of opioid and alcohol dependence. Pharmacogenetics and genomics 39 19801958
2007 Phosphorylation of IRF8 in a pre-associated complex with Spi-1/PU.1 and non-phosphorylated Stat1 is critical for LPS induction of the IL1B gene. Molecular immunology 39 17386941
2012 Effect of Porphyromonas gingivalis and Lactobacillus acidophilus on secretion of IL1B, IL6, and IL8 by gingival epithelial cells. Inflammation 38 22382516
2013 Polymorphisms of genes encoding P2X7R, IL-1B, OPG and RANK in orthodontic-induced apical root resorption. Oral diseases 37 24118270
2012 Capsaicin consumption, Helicobacter pylori CagA status and IL1B-31C>T genotypes: a host and environment interaction in gastric cancer. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 37 22414649
2022 Curcumin-Attenuated TREM-1/DAP12/NLRP3/Caspase-1/IL1B, TLR4/NF-κB Pathways, and Tau Hyperphosphorylation Induced by 1,2-Diacetyl Benzene: An in Vitro and in Silico Study. Neurotoxicity research 36 35781221
2020 Influence of inflammasome NLRP3, and IL1B and IL2 gene polymorphisms in periodontitis susceptibility. PloS one 36 31978095
2012 Differential expression of gastric MUC5AC in colonic epithelial cells: TFF3-wired IL1 β/Akt crosstalk-induced mucosal immune response against Shigella dysenteriae infection. Journal of cell science 36 22389405
2012 Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case-control study. BMC infectious diseases 36 23148654
2008 IL6 and IL1B polymorphisms are associated with fat mass in older men: the MrOS Study Sweden. Obesity (Silver Spring, Md.) 36 18239554
2008 The relationship between ApoE, TNFA, IL1a, IL1b and IL12b genes and HIV-1-associated dementia. HIV medicine 36 18631256
2009 Analysis of the association of IL1B (C+3954T) and IL1RN (intron 2) polymorphisms with dental implant loss in a Brazilian population. Clinical oral implants research 35 19191798
2012 IL1B, IL4R, IL12RB1 and TNF gene polymorphisms are associated with Plasmodium vivax malaria in Brazil. Malaria journal 34 23217179
2011 Interleukin 1 beta (IL1B) promoter polymorphism and cancer risk: evidence from 47 published studies. Mutagenesis 33 21653279
2004 Haplotype structure of inflammatory cytokines genes (IL1B, IL6 and TNF/LTA) in US Caucasians and African Americans. Genes and immunity 33 15306845
2018 Tryptophan Photoproduct FICZ Upregulates IL1A, IL1B, and IL6 Expression via Oxidative Stress in Keratinocytes. Oxidative medicine and cellular longevity 32 30595799
2016 Variants in LTA, TNF, IL1B and IL10 genes associated with the clinical course of sepsis. Immunologic research 32 27592234
1991 Haemodialysis membranes modulate chronically the production of TNF alpha, IL1 beta and IL6. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 32 1775252
2019 Increased levels of plasma IL-1b and BDNF can predict resistant depression patients. Revista da Associacao Medica Brasileira (1992) 29 30994834
2015 Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population. Schizophrenia research 29 26481614
2010 Association of IL1A and IL1B loci with primary open angle glaucoma. BMC medical genetics 29 20565898
2022 Integrated Bioinformatics and Validation Reveal IL1B and Its Related Molecules as Potential Biomarkers in Chronic Spontaneous Urticaria. Frontiers in immunology 28 35371000
2018 Distinct mechanisms regulate IL1B gene transcription in lymphoid CD4 T cells and monocytes. Cytokine 28 30300855
2024 Single-cell profiling identifies IL1Bhi macrophages associated with inflammation in PD-1 inhibitor-induced inflammatory arthritis. Nature communications 27 38453911
2021 IL-1B(3954) polymorphism and red complex bacteria increase IL-1β (GCF) levels in periodontitis. Journal of periodontal research 26 33638191
2017 Association between TNF, IL1B, IL6, IL10 and IFNG polymorphisms and recurrent miscarriage: a case control study. Reproductive biology and endocrinology : RB&E 26 29017513
2007 Potential influence of IL1B haplotype and IL1A-IL1B-IL1RN extended haplotype on hand osteoarthritis risk. Osteoarthritis and cartilage 26 17532232
2020 Association between IL1B polymorphisms and the risk of rheumatoid arthritis. International immunopharmacology 24 32240943
2016 Association of Neuropeptide-Y (NPY) and Interleukin-1beta (IL1B), Genotype-Phenotype Correlation and Plasma Lipids with Type-II Diabetes. PloS one 24 27749914
2015 SNP interactions of Helicobacter pylori-related host genes PGC, PTPN11, IL1B, and TLR4 in susceptibility to gastric carcinogenesis. Oncotarget 24 26158864
2014 Genetic polymorphism of interleukin-1A (IL-1A), IL-1B, and IL-1 receptor antagonist (IL-1RN) and prostate cancer risk. Asian Pacific journal of cancer prevention : APJCP 24 25374200
2007 Functional polymorphism of thymidylate synthase, but not of the COMT and IL-1B genes, is associated with breast cancer. Journal of clinical laboratory analysis 24 17385677
2019 Association between IL1B gene and cervical cancer susceptibility in Chinese Uygur Population: A Case-Control study. Molecular genetics & genomic medicine 23 31222982
2023 TNF-α, IL-1B and IL-6 affect the differentiation ability of dental pulp stem cells. BMC oral health 22 37568110
2010 Association of interleukin-1beta (IL1B) polymorphisms with Graves' ophthalmopathy in Taiwan Chinese patients. Investigative ophthalmology & visual science 22 20671275
2008 Association of IL-1B gene polymorphisms with nasopharyngeal carcinoma in a Chinese population. Clinical oncology (Royal College of Radiologists (Great Britain)) 22 18289837
2008 Polymorphisms in two genes, IL-1B and ACE, are associated with erythropoietin resistance in Korean patients on maintenance hemodialysis. Experimental & molecular medicine 21 18446054
2021 Monocyte-derived and M1 macrophages from ankylosing spondylitis patients released higher TNF-α and expressed more IL1B in response to BzATP than macrophages from healthy subjects. Scientific reports 20 34497300
2014 Association between the IL1B, IL1RN polymorphisms and COPD risk: a meta-analysis. Scientific reports 20 25174605
2008 Intracellular HMGB1 transactivates the human IL1B gene promoter through association with an Ets transcription factor PU.1. European journal of haematology 20 18173740
2006 A polymorphism of C-to-T substitution at -31 IL1B is associated with the risk of advanced gastric adenocarcinoma in a Japanese population. Journal of human genetics 20 17006606
2023 Sijunzi Decoction Targets IL1B and TNF to Reduce Neutrophil Extracellular Traps (NETs) in Ulcerative Colitis: Evidence from Silicon Prediction and Experiment Validation. Drug design, development and therapy 19 37868820
2021 Long non-coding RNA MIAT impairs neurological function in ischemic stroke via up-regulating microRNA-874-3p-targeted IL1B. Brain research bulletin 19 34265390
2020 Genetic polymorphisms in the Interleukins IL1B, IL4, and IL6 are associated with concomitant periodontitis and type 2 diabetes mellitus in Brazilian patients. Journal of periodontal research 19 32648256
2020 IL1B triggers inflammatory cytokine production in bovine oviduct epithelial cells and induces neutrophil accumulation via CCL2. American journal of reproductive immunology (New York, N.Y. : 1989) 19 33099841
2019 Interleukin-1β Gene (IL1B) Polymorphism and Risk of Developing Diabetic Nephropathy. Immunological investigations 19 31044637
2016 Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms. Alimentary pharmacology & therapeutics 19 27730688
2012 Variation in the IL1B, TNF and IL6 genes and individual susceptibility to prosthetic joint infection. BMC immunology 19 22568934
2011 Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib. Annals of hematology 19 21347685
2010 Interleukin 1 beta (IL1B) gene polymorphisms are not associated with gastric carcinogenesis in Germany. Anticancer research 19 20332462
2019 Are IL1B, IL6 and IL6R Gene Variants Associated with Anterior Cruciate Ligament Rupture Susceptibility? Journal of sports science & medicine 18 30787661
2019 Genetic polymorphisms in IL1B predict susceptibility to steroid-induced osteonecrosis of the femoral head in Chinese Han population. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 18 30852631
2015 Lipocalin 2 Upregulation Protects Hepatocytes from IL1-β-Induced Stress. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 18 26021263
2024 The role of IL-1B in breast cancer bone metastasis. Journal of bone oncology 17 38800348
2020 NAT1 promotes osteolytic metastasis in luminal breast cancer by regulating the bone metastatic niche via NF-κB/IL-1B signaling pathway. American journal of cancer research 17 32905535
2017 A link between osteomyelitis and IL1RN and IL1B polymorphisms-a study in patients from Northeast Brazil. Acta orthopaedica 17 28682145
2014 Interleukin 1B gene (IL1B) variation and internalizing symptoms in maltreated preschoolers. Development and psychopathology 17 25422961
2011 IL1B -511(G>A) and IL1RN (VNTR) allelic polymorphisms and susceptibility to knee osteoarthritis in Croatian population. Rheumatology international 17 21523343
2020 Evaluation of genetic variants in IL-1B and its interaction with the predisposition of osteoporosis in the northwestern Chinese Han population. The journal of gene medicine 16 32391643
2017 Flavonolignans Inhibit IL1-β-Induced Cross-Talk between Blood Platelets and Leukocytes. Nutrients 16 28914761
2011 Initial interrogation, confirmation and fine mapping of modifying genes: STAT3, IL1B and IFNGR1 determine cystic fibrosis disease manifestation. European journal of human genetics : EJHG 16 21731057
2009 IL1B promoter polymorphism regulates the expression of gastric acid stimulating hormone gastrin. The international journal of biochemistry & cell biology 16 19166966
2001 Association analysis of IL1A and IL1B variants in alopecia areata. Heredity 16 11703512
2024 BaP/BPDE exposure causes human trophoblast cell dysfunctions and induces miscarriage by up-regulating lnc-HZ06-regulated IL1B. Journal of hazardous materials 15 38991640
2013 Current evidences on IL1B polymorphisms and lung cancer susceptibility: a meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 23784458
2008 Allele-specific induction of IL1B -31T/C promoter polymorphism by lung carcinogens. Mutation research 15 18656550
2006 Association of IL1B polymorphisms with gastric cancer in a Chinese population. Clinical biochemistry 15 17196954
2018 The Serum Level of IL-1B Correlates with the Activity of Chronic Pulmonary Aspergillosis. Canadian respiratory journal 14 30363691
2015 Contribution of IL6 -174 G>C and IL1B +3954 C>T polymorphisms to congenital infection with Toxoplasma gondii. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 14 26385345
2013 Polymorphisms of the IL12B, IL1B, and TNFA genes and susceptibility to asthma. Journal of investigational allergology & clinical immunology 14 24654313