Affinage

IL1A

Interleukin-1 alpha · UniProt P01583

Round 2 corrected
Length
271 aa
Mass
30.6 kDa
Annotated
2026-04-28
130 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-1α is a pleiotropic pro-inflammatory cytokine synthesized as a 271-amino-acid leaderless precursor (pro-IL-1α) that operates through three distinct modes: as an intracrine nuclear transcriptional activator via its N-terminal pro-piece containing a nuclear localization sequence, as a cell-surface juxtacrine signal that engages the IL-1RI/IL-1RAcP receptor complex to activate NF-κB and C/EBPβ, and as a mature secreted cytokine released upon apoptosis or cathepsin G cleavage (PMID:14983027, PMID:19805069, PMID:29976772). Cell-surface IL-1α is the master upstream regulator of the senescence-associated secretory phenotype (SASP), driving IL-6 and IL-8 transcription through IRAK1–NF-κB signaling, with its translation selectively controlled by mTORC1 and its locus-specific transcription epigenetically regulated by DOT1L-mediated H3K79 methylation downstream of STING (PMID:19805069, PMID:26147250, PMID:34037658). Unconventional secretion of pro-IL-1α depends on caspase-1 activity without pro-IL-1α being a direct caspase-1 substrate, and the ternary IL-1/IL-1RI/IL-1RAcP signaling complex assembles through a stepwise mechanism in which agonist and antagonist ligands make structurally distinguishable receptor contacts (PMID:18329368, PMID:22426547, PMID:37315560).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1984 High

    Cloning of the murine IL-1α precursor and demonstration that the C-terminal ~156 residues constitute the biologically active domain established the fundamental domain architecture of the cytokine.

    Evidence cDNA cloning with E. coli expression and truncation bioassays

    PMID:6209582

    Open questions at the time
    • Function of the N-terminal pro-piece unknown
    • Processing protease(s) unidentified
    • Receptor identity unknown
  2. 1985 High

    Independent cloning of human IL-1α and IL-1β from macrophage libraries resolved the longstanding question of IL-1 heterogeneity, proving two distinct genes encode proteins with overlapping bioactivities.

    Evidence cDNA cloning of both genes, E. coli expression, and parallel bioassays

    PMID:2989698 PMID:2994016

    Open questions at the time
    • Whether the two forms signal through the same or different receptors unresolved
    • Secretion mechanism for leaderless IL-1α unknown
  3. 1986 High

    Competitive binding studies demonstrated that IL-1α and IL-1β share an identical ~80 kDa cell-surface receptor, establishing the shared receptor paradigm for the IL-1 family.

    Evidence Radiolabeled ligand competition and cross-linking on murine and human cells

    PMID:2946959 PMID:3485152

    Open questions at the time
    • Receptor cDNA not yet cloned
    • Accessory proteins for signaling not identified
  4. 1988 High

    Molecular cloning of the IL-1 receptor from T cells revealed a single-pass transmembrane protein with three Ig-like extracellular domains, placing IL-1 signaling within the immunoglobulin superfamily.

    Evidence Expression cloning from murine T cells with radiolabeled IL-1α/β binding validation

    PMID:2969618

    Open questions at the time
    • Accessory chain(s) for signal transduction not identified
    • Intracellular signaling mechanism unknown
  5. 1991 High

    Distinguishing apoptotic from necrotic release showed that IL-1α is processed and released during apoptosis whereas necrosis releases predominantly unprocessed pro-IL-1α, establishing cell death mode as a determinant of IL-1α bioactivity.

    Evidence Apoptosis (CTL-mediated) vs. necrosis induction with Western blot for pro/mature forms

    PMID:1924307

    Open questions at the time
    • Identity of the intracellular protease(s) mediating apoptotic processing unknown
    • Whether necrotic release of pro-IL-1α has biological activity in vivo unclear
  6. 2004 High

    Demonstration that pro-IL-1α functions as an intracrine transcriptional activator—translocating to the nucleus and activating NF-κB/AP-1 independently of IL-1 receptor engagement—revealed a receptor-independent signaling mode residing in the N-terminal pro-piece/NLS.

    Evidence Overexpression with IL-1Ra receptor blockade, GAL4 reporter, NF-κB/AP-1 reporters, cytokine secretion

    PMID:14983027

    Open questions at the time
    • Nuclear binding partners/chromatin targets of pro-IL-1α unidentified
    • Physiological contexts where intracrine function dominates over paracrine unclear
  7. 2008 High

    Caspase-1 was shown to be required for unconventional secretion of pro-IL-1α without being its direct protease, revealing a non-canonical secretion pathway shared with other leaderless proteins like FGF-2.

    Evidence Caspase-1 KO and pharmacologic inhibition, co-IP of pro-IL-1α with FGF-2, iTRAQ secretome proteomics

    PMID:18329368

    Open questions at the time
    • Molecular mechanism by which caspase-1 promotes secretion of non-substrates unresolved
    • Vesicular vs. non-vesicular route of export not determined
  8. 2009 High

    Cell-surface IL-1α was identified as the essential upstream initiator of the SASP, acting through IL-1RI/IRAK1/NF-κB/C/EBPβ to drive IL-6 and IL-8 transcription in senescent cells, thus positioning IL-1α as the master regulator of senescence-associated inflammation.

    Evidence siRNA, neutralizing antibody, IL-1Ra blockade across multiple senescence models; IRAK1 knockdown

    PMID:19805069

    Open questions at the time
    • Regulation of IL-1α surface presentation during senescence not characterized
    • Whether intracrine IL-1α also contributes to SASP gene induction not separated
  9. 2012 High

    The crystal structure of the IL-1β/IL-1RI/IL-1RAcP ternary complex established the stepwise assembly mechanism for IL-1 signaling and provided the structural basis for distinguishing agonist from antagonist receptor binding.

    Evidence X-ray crystallography of the heterotrimeric complex

    PMID:22426547

    Open questions at the time
    • No ternary structure with IL-1α as the ligand available
    • Structural basis of IL-1α vs. IL-1β selectivity at IL-1RI not resolved at atomic level
  10. 2015 High

    mTORC1 was identified as the selective translational controller of IL-1α during senescence, explaining how nutrient-sensing pathways regulate SASP amplitude—rapamycin suppressed IL-1α translation, NF-κB activity, and tumor-promoting effects of senescent cells in vivo.

    Evidence Rapamycin treatment with IL-1α rescue, NF-κB assays, mouse xenograft tumor model

    PMID:26147250

    Open questions at the time
    • Specific mRNA cis-elements or trans-factors linking mTORC1 to IL1A translation not identified
    • Whether mTORC1 control is unique to senescence or operates in other IL-1α-producing contexts unknown
  11. 2018 Medium

    Cathepsin G present in neutrophil extracellular traps (NETs) was identified as a protease that processes pro-IL-1α to its active mature form, mediating NET-induced endothelial activation and tissue factor expression specifically through IL-1α rather than IL-1β.

    Evidence Neutralizing antibodies distinguishing IL-1α from IL-1β, cathepsin G inhibition, endothelial activation assays

    PMID:29976772

    Open questions at the time
    • Cathepsin G cleavage site in pro-IL-1α not mapped at amino acid level
    • Relative contribution of cathepsin G vs. other proteases in vivo not established
  12. 2021 Medium

    DOT1L was found to epigenetically regulate IL1A transcription during oncogene-induced senescence by depositing H3K79me2/3 at the IL1A locus downstream of STING, providing the first locus-specific epigenetic writer controlling SASP initiation.

    Evidence ChIP-seq, DOT1L knockdown/overexpression, STING pathway perturbation

    PMID:34037658

    Open questions at the time
    • Mechanism linking STING activation to DOT1L recruitment at IL1A locus not defined
    • Whether DOT1L regulation of IL1A operates outside senescence contexts unknown
  13. 2023 Medium

    A human IL-1R1 missense variant (K131E) that selectively abolishes IL-1Ra binding while preserving IL-1α/β agonist binding provided genetic proof that structurally distinct receptor contacts separate agonist from antagonist engagement, with functional validation in a knock-in mouse model showing hyperinflammation.

    Evidence Patient genetics, binding assays, knock-in mouse model, arthritis model

    PMID:37315560

    Open questions at the time
    • No ternary crystal structure with IL-1α to confirm predicted contact differences
    • Single family — broader allelic spectrum at IL-1R1 not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the nuclear binding partners and chromatin targets of the intracrine pro-IL-1α pro-piece, the structural basis of IL-1α (vs. IL-1β) selectivity at the receptor at atomic resolution, and the precise vesicular or non-vesicular mechanism by which caspase-1 facilitates IL-1α unconventional secretion.
  • No atomic-resolution structure of IL-1α bound to IL-1RI/IL-1RAcP
  • Intracrine nuclear targets of pro-IL-1α pro-piece unidentified
  • Mechanism of caspase-1-dependent unconventional secretion of non-substrate cargo unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005576 extracellular region 3 GO:0005634 nucleus 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1640170 Cell Cycle 2
Partners
CASP1CTSGDOT1LFGF2IL1R1IL1RAP

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 IL-1α and IL-1β are encoded by two distinct but distantly related cDNAs isolated from a macrophage library; the primary translation products are 271 and 269 amino acids, respectively, and the carboxy-terminal portions (~153-159 aa) expressed in E. coli are sufficient to confer IL-1 biological activity. cDNA cloning, E. coli expression, biological activity assay Nature High 2989698
1984 Murine IL-1 (IL-1α ortholog) is encoded by a 270-amino-acid precursor; the carboxy-terminal 156 amino acids expressed in E. coli yield biologically active IL-1, establishing the domain architecture of the precursor. cDNA cloning, E. coli expression, biological activity assay Nature High 6209582
1985 Human IL-1α precursor (preIL-1α) consists of 271 amino acid residues; expression of the cloned human cDNA in E. coli yields biologically active IL-1α, confirming its distinct gene identity from IL-1β. cDNA cloning, E. coli expression, biological activity assay Nucleic acids research High 2994016
1986 Recombinant human IL-1α (carboxy-terminal 154 amino acids) purified to homogeneity stimulates T cell and fibroblast proliferation and induces fibroblast collagenase and prostaglandin production, proving a single IL-1α molecule mediates multiple previously described IL-1 activities. E. coli expression, protein purification, multiple cell-based bioassays Journal of immunology High 3485152
1986 IL-1α and IL-1β share an identical cell-surface receptor (~80 kDa) on murine T cells and fibroblasts and on human cells, as determined by competitive binding studies. Radiolabeled ligand binding, competition assay, cross-linking Nature High 2946959
1988 The IL-1 receptor (binding both IL-1α and IL-1β) was cloned from mouse T cells; its extracellular domain is 319 amino acids organized in three immunoglobulin-like domains and its cytoplasmic domain is 217 amino acids, placing it in the immunoglobulin superfamily. cDNA expression cloning, binding assay with radiolabeled IL-1α and IL-1β Science High 2969618
1990 Internalized IL-1α remains bound to its receptor intracellularly for at least 4 hours without degradation and accumulates in purified nuclei, demonstrating IL-1α-driven translocation of the cell-surface IL-1 receptor complex to the nucleus. 125I-IL-1α binding, electron microscope autoradiography, subcellular fractionation Journal of immunology Medium 2137488
1991 IL-1α is processed and released during apoptosis: when cells undergo apoptosis triggered by allospecific cytotoxic T lymphocytes, both IL-1α and IL-1β are efficiently matured intracellularly, whereas necrosis releases IL-1α as a mixture of unprocessed and processed forms with IL-1β remaining as inactive pro-form. Cell death assays (apoptosis vs. necrosis induction), Western blot for pro- vs. mature IL-1 forms Proceedings of the National Academy of Sciences of the United States of America High 1924307
1994 A physical map of the human IL-1 gene cluster places IL1A, IL1B, and IL1RN within an ~430 kb restriction fragment, with IL1A located between 0–35 kb from one terminal CpG island, IL1B between 70–110 kb, and IL1RN between 330–430 kb. Pulsed-field gel electrophoresis, Southern blotting with gene-specific probes Genomics High 8188271
2004 The precursor form of IL-1α (pro-IL-1α) functions as an intracrine transcriptional activator: it translocates to the nucleus upon TLR ligand stimulation and, independently of IL-1 receptor signaling, activates NF-κB, AP-1, and transcription of IL-8 and IL-6. The transcriptional activation activity resides in the N-terminal pro-piece containing the nuclear localization sequence, not in the C-terminal mature form. Overexpression with IL-1Ra blockade to prevent receptor signaling, GAL4 reporter system, NF-κB/AP-1 reporter assays, cytokine secretion measurement, intracellular localization imaging Proceedings of the National Academy of Sciences of the United States of America High 14983027
2008 Caspase-1 activity is required for unconventional secretion of pro-IL-1α (as well as FGF-2 and caspase-1 itself) even though pro-IL-1α is not a direct proteolytic substrate of caspase-1; physical interaction between pro-IL-1α and FGF-2 was demonstrated, and iTRAQ proteomics identified additional leaderless proteins whose secretion depends on caspase-1. Caspase-1 inhibition/knockout, co-immunoprecipitation (physical interaction), iTRAQ secretome proteomics Cell High 18329368
2009 Cell surface-bound IL-1α (not secreted IL-1α) is the essential upstream regulator of the senescence-associated secretory phenotype (SASP): senescent fibroblasts express high IL-1α mRNA and intracellular/surface protein but secrete little; IL-1Ra, neutralizing anti-IL-1α antibody, or IL-1α siRNA markedly reduced IL-6 and IL-8 secretion. The mechanism involves IL-1α engaging the IL-1 receptor to activate IRAK1, NF-κB, and C/EBPβ, which drive IL-6/IL-8 transcription. IL-1α also controls the invasiveness-promoting activity of senescent cell conditioned medium. RNA interference, neutralizing antibody, IL-1Ra blockade, NF-κB/C/EBPβ DNA-binding assays, IRAK1 knockdown, multiple senescence induction models Proceedings of the National Academy of Sciences of the United States of America High 19805069
2012 Crystal structure of the IL-1β/IL-1RI/IL-1RAcP heterotrimeric signaling complex reveals a stepwise assembly mechanism where IL-1 binds its primary receptor (IL-1RI), which then recruits the accessory protein IL-1RAcP, bringing TIR domains into proximity to initiate NF-κB signaling; structural analysis also reveals evolutionary relationship with the fibroblast growth factor receptor family. X-ray crystallography of the ternary complex Nature structural & molecular biology High 22426547
2015 mTORC1 selectively regulates pro-inflammatory SASP by promoting IL-1α translation: rapamycin reduced overall cytokine mRNA levels, but specifically suppressed translation of membrane-bound IL-1α. Reduced IL-1α diminished NF-κB transcriptional activity controlling much of the SASP, and exogenous IL-1α restored IL-6 secretion to rapamycin-treated senescent cells. Rapamycin also suppressed the ability of senescent fibroblasts to stimulate prostate tumor growth in mice. Rapamycin treatment, IL-1α rescue experiment, NF-κB activity assay, cytokine secretion measurement, mouse xenograft tumor model Nature cell biology High 26147250
2007 Intratesticular administration of IL-1α disrupts the blood-testis barrier (BTB) and Sertoli-germ cell adhesion without reducing steady-state levels of BTB proteins (OCLN, CLDN1, F11R, TJP1, CDH2); instead, IL-1α alters the localization of OCLN, F11R, and TJP1 away from cell-cell contact sites and perturbs filamentous actin organization at the BTB and apical ectoplasmic specialization, indicating the Sertoli cell actin cytoskeleton is the primary cellular target of IL-1α in BTB restructuring. Intratesticular injection in rats, inulin-FITC permeability assay, immunofluorescence localization, Western blot, F-actin staining Biology of reproduction Medium 18057314
2018 The age-associated decline of DNMT3A in hematopoietic cells enhances IL-1α production; IL-1α from myeloid progenitor-like cells drives enhanced emergency myelopoiesis in aging, promotes lung cancer progression, and disrupting IL-1R1 signaling early in tumor development normalized myelopoiesis and slowed growth of lung, colonic, and pancreatic tumors. Genetic mouse models (DNMT3A manipulation, IL-1R1 deletion), scRNA-seq, in vivo tumor models Science Medium 39236155
2021 DOT1L, a H3K79 methyltransferase, epigenetically regulates IL1A gene expression during oncogene-induced senescence (OIS): DOT1L is necessary and sufficient for increased H3K79me2/3 occupancy specifically at the IL1A gene locus (but not other SASP genes), downstream of STING activation, thereby controlling IL-1α-driven SASP without affecting senescence-associated cell cycle arrest. ChIP-seq, DOT1L knockdown/overexpression, STING pathway manipulation, IL1A promoter occupancy assays The Journal of cell biology Medium 34037658
2018 NETs promote endothelial cell (EC) activation and tissue factor production through IL-1α: anti-IL-1α neutralizing antibody (but not anti-IL-1β) blocked NET-induced VCAM-1, ICAM-1, and tissue factor expression. Cathepsin G (abundant in NETs) potentiates this by cleaving pro-IL-1α to release the more potent mature IL-1α form. Neutralizing antibodies, cathepsin G inhibition, mRNA and protein expression assays, clotting assays in cell-free and EC systems Arteriosclerosis, thrombosis, and vascular biology Medium 29976772
2023 A de novo missense variant in IL-1R1 (p.Lys131Glu) identified in a CRMO patient disrupts binding of the antagonist ligand IL-1Ra but preserves binding of IL-1α and IL-1β, resulting in unopposed IL-1 signaling. Mice with the homologous mutation showed hyperinflammation and enhanced collagen antibody-induced arthritis with pathological osteoclastogenesis, establishing that differential receptor contacts distinguish agonist (IL-1α/IL-1β) from antagonist (IL-1Ra) binding. Patient genetics, binding assays, knock-in mouse model, arthritis model, structural inference Immunity Medium 37315560
2023 Aging-associated IL-1 elevation in the bone marrow drives IL-1R1-dependent expansion of Tet2+/− hematopoietic stem and progenitor cells (HSPCs) by increasing cell cycle progression, multilineage differentiation, and repopulation capacity; genetic deletion of IL-1R1 specifically in Tet2+/− HSPCs or pharmacologic IL-1 inhibition impaired Tet2+/− clonal expansion, establishing IL-1 pathway as a mechanistic driver of TET2-mutant clonal hematopoiesis. Bone marrow transplantation, genetic mosaicism mouse models, IL-1R1 conditional deletion, IL-1α administration, transcriptomic analysis Blood Medium 36379023
2021 IL-1α secreted by tumor cells engages IL-1R1 on pancreatic stellate cells (PSCs) as an upstream mediator of IL-6 release, which in turn activates STAT3 in tumor cells; IL-1R1 inhibition with anakinra reduced stromal IL-6 and STAT3 activation in human PDAC cell lines and in a genetic mouse model, and combination with chemotherapy extended survival. Co-culture experiments, IL-1R1 blockade (anakinra), genetic mouse model (PKT), STAT3 activity assays, survival analysis Molecular cancer therapeutics Medium 34518296

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomatic medicine 2179 19188531
1985 Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature 1766 2989698
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
2018 Overview of the IL-1 family in innate inflammation and acquired immunity. Immunological reviews 1403 29247995
1997 MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1. Nature 1121 9020361
1984 Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. Nature 978 6209582
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2015 MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nature cell biology 903 26147250
2006 The P2X7 receptor: a key player in IL-1 processing and release. Journal of immunology (Baltimore, Md. : 1950) 872 16547218
1988 cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily. Science (New York, N.Y.) 863 2969618
2010 Disease-associated functions of IL-33: the new kid in the IL-1 family. Nature reviews. Immunology 822 20081870
2008 Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nature genetics 817 18583979
2010 Interleukin-1 (IL-1) pathway. Science signaling 765 20086235
2010 IL-1 pathways in inflammation and human diseases. Nature reviews. Rheumatology 715 20177398
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2008 Active caspase-1 is a regulator of unconventional protein secretion. Cell 702 18329368
2018 NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis. Circulation research 697 29880500
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Genome-scale RNAi screen for host factors required for HIV replication. Cell host & microbe 627 18976975
2002 The balance between IL-1 and IL-1Ra in disease. Cytokine & growth factor reviews 576 12220547
1995 Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 572 7566121
2009 Cell surface-bound IL-1alpha is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. Proceedings of the National Academy of Sciences of the United States of America 532 19805069
2002 The IL-1 family and inflammatory diseases. Clinical and experimental rheumatology 502 14989423
1986 The cell surface receptors for interleukin-1 alpha and interleukin-1 beta are identical. Nature 467 2946959
2015 Widespread macromolecular interaction perturbations in human genetic disorders. Cell 454 25910212
2002 Lipopolysaccharide-mediated reactive oxygen species and signal transduction in the regulation of interleukin-1 gene expression. The Journal of biological chemistry 440 11940570
1991 Interleukin 1 is processed and released during apoptosis. Proceedings of the National Academy of Sciences of the United States of America 440 1924307
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2016 Interleukin 1α and the inflammatory process. Nature immunology 437 27434011
2000 Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nature cell biology 436 10854325
2004 Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription. The Journal of biological chemistry 317 15489227
1989 Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins. The American journal of physiology 314 2784290
2006 Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium. The Lancet. Oncology 313 16389181
2004 The precursor form of IL-1alpha is an intracrine proinflammatory activator of transcription. Proceedings of the National Academy of Sciences of the United States of America 299 14983027
1992 Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis. The American journal of pathology 298 1739124
1997 Phenotypic and functional characterization of mice that lack the type I receptor for IL-1. Journal of immunology (Baltimore, Md. : 1950) 297 9317135
1989 Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1. Proceedings of the National Academy of Sciences of the United States of America 295 2536171
2016 IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis. The Journal of allergy and clinical immunology 293 28043870
2018 Neutrophil Extracellular Traps Induce Endothelial Cell Activation and Tissue Factor Production Through Interleukin-1α and Cathepsin G. Arteriosclerosis, thrombosis, and vascular biology 283 29976772
1986 Recombinant human interleukin 1 alpha: purification and biological characterization. Journal of immunology (Baltimore, Md. : 1950) 282 3485152
1994 A physical map of the region encompassing the human interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes. Genomics 281 8188271
2000 Four new members expand the interleukin-1 superfamily. The Journal of biological chemistry 276 10625660
2000 Identification and initial characterization of four novel members of the interleukin-1 family. The Journal of biological chemistry 275 10744718
1985 Cloning and characterization of the cDNAs for human and rabbit interleukin-1 precursor. Nucleic acids research 270 2994016
2019 The IL-1 family of cytokines and receptors in rheumatic diseases. Nature reviews. Rheumatology 265 31515542
2003 Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling. The EMBO journal 239 14633987
2019 Structural Basis of IL-1 Family Cytokine Signaling. Frontiers in immunology 231 31281320
2000 IL-1 receptor-associated kinase modulates host responsiveness to endotoxin. Journal of immunology (Baltimore, Md. : 1950) 219 10754329
2012 Caspase-1: is IL-1 just the tip of the ICEberg? Cell death & disease 217 22764097
1998 IL-1 produced and released endogenously within human islets inhibits beta cell function. The Journal of clinical investigation 211 9691088
2014 The role IL-1 in tumor-mediated angiogenesis. Frontiers in physiology 188 24734023
1996 A20 zinc finger protein inhibits TNF and IL-1 signaling. Journal of immunology (Baltimore, Md. : 1950) 185 8557994
2014 LPS and IL-1 differentially activate mouse and human astrocytes: role of CD14. Glia 171 24659539
1990 IL-1 and its receptor are translocated to the nucleus. Journal of immunology (Baltimore, Md. : 1950) 171 2137488
1998 Sleep. A physiologic role for IL-1 beta and TNF-alpha. Annals of the New York Academy of Sciences 160 9917875
2014 The TLR and IL-1 signalling network at a glance. Journal of cell science 158 24829146
2004 Therapeutic strategies to reduce IL-1 activity in treating local and systemic inflammation. Current opinion in pharmacology 153 15251132
2004 T1/ST2--an IL-1 receptor-like modulator of immune responses. Cytokine & growth factor reviews 145 15110792
2014 IL-1 signaling in obesity-induced hepatic lipogenesis and steatosis. PloS one 134 25216251
2006 IL-1 receptor antagonist in metabolic diseases: Dr Jekyll or Mr Hyde? FEBS letters 134 17097645
2018 Hepatocyte-specific deletion of IL1-RI attenuates liver injury by blocking IL-1 driven autoinflammation. Journal of hepatology 122 29366909
2009 Regulating human Th17 cells via differential expression of IL-1 receptor. Blood 122 19965648
2023 Aging drives Tet2+/- clonal hematopoiesis via IL-1 signaling. Blood 119 36379023
1994 The IL-1 receptor signaling pathway. Journal of leukocyte biology 118 7964161
2009 IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide. American journal of respiratory and critical care medicine 114 19234101
1989 Activated platelets express IL-1 activity. Journal of immunology (Baltimore, Md. : 1950) 111 2592766
2015 Mechanisms of unconventional secretion of IL-1 family cytokines. Cytokine 108 25922276
2004 Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. Genes and immunity 104 15190266
2015 IL-1 in Colon Inflammation, Colon Carcinogenesis and Invasiveness of Colon Cancer. Cancer microenvironment : official journal of the International Cancer Microenvironment Society 102 26686225
2024 Hematopoietic aging promotes cancer by fueling IL-1⍺-driven emergency myelopoiesis. Science (New York, N.Y.) 99 39236155
2012 Structure of the activating IL-1 receptor signaling complex. Nature structural & molecular biology 97 22426547
2020 The IL-1 family cytokines and receptors in autoimmune diseases. Autoimmunity reviews 95 32663626
1996 Interleukin 1 (IL1) and tumour necrosis factor (TNF) signal transduction. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 89 8650261
1998 Biologic activities of IL-1 and its role in human disease. The Journal of allergy and clinical immunology 86 9768571
2012 Inflammasome activation of IL-1 family mediators in response to cutaneous photodamage. Photochemistry and photobiology 85 22631445
2020 IL-1 Signaling in Tumor Microenvironment. Advances in experimental medicine and biology 80 32060884
2016 IL-1 Inhibition and Vascular Function in CKD. Journal of the American Society of Nephrology : JASN 79 27647856
2013 Negative regulatory receptors of the IL-1 family. Seminars in immunology 77 24239046
2013 Autophagy and IL-1 Family Cytokines. Frontiers in immunology 75 23577011
2008 Gamendazole, an orally active indazole carboxylic acid male contraceptive agent, targets HSP90AB1 (HSP90BETA) and EEF1A1 (eEF1A), and stimulates Il1a transcription in rat Sertoli cells. Biology of reproduction 71 18218611
1991 Chromosomal location of murine and human IL-1 receptor genes. Genomics 71 1672292
2020 IL-1 Superfamily Members and Periodontal Diseases. Journal of dental research 69 32758110
2017 Inflammasomes and IL-1 biology in the pathogenesis of allograft dysfunction. The Journal of clinical investigation 69 28569730
2007 Interleukin 1 alpha (IL1A) is a novel regulator of the blood-testis barrier in the rat. Biology of reproduction 69 18057314
2002 Regulation of IL-1 receptor-associated kinases by lipopolysaccharide. Journal of immunology (Baltimore, Md. : 1950) 67 11937546
1989 Rabbit IL-1. Cloning, expression, biologic properties, and transcription during endotoxemia. Journal of immunology (Baltimore, Md. : 1950) 67 2784458
2021 The Immunological Impact of IL-1 Family Cytokines on the Epidermal Barrier. Frontiers in immunology 65 35003136
2004 Anakinra: an inhibitor of IL-1 for the treatment of rheumatoid arthritis. Expert opinion on biological therapy 64 15268666
2017 IL-1 family cytokines in cardiovascular disease. Cytokine 62 29198612
1999 TNF alpha and IL-1 beta are separate targets in chronic arthritis. Clinical and experimental rheumatology 62 10589368
2021 IL-1 Family Antagonists in Mouse and Human Skin Inflammation. Frontiers in immunology 61 33796114
2023 Identification of an IL-1 receptor mutation driving autoinflammation directs IL-1-targeted drug design. Immunity 57 37315560
2018 The role of IL-1 in gout: from bench to bedside. Rheumatology (Oxford, England) 57 29272514
2000 T6BP, a TRAF6-interacting protein involved in IL-1 signaling. Proceedings of the National Academy of Sciences of the United States of America 56 10920205
2005 Central IL-1 receptor signaling regulates bone growth and mass. Proceedings of the National Academy of Sciences of the United States of America 54 16126903
2003 Association of IL1A gene polymorphisms with susceptibility to and severity of systemic sclerosis in the Japanese population. Arthritis and rheumatism 53 12528118
1991 IL-1 beta and prostaglandins regulate integrin mRNA expression. Journal of cellular physiology 53 1748714
1990 Binding of IL-1 beta to alpha-macroglobulins and release by thioredoxin. Journal of immunology (Baltimore, Md. : 1950) 53 1700994
2021 DOT1L modulates the senescence-associated secretory phenotype through epigenetic regulation of IL1A. The Journal of cell biology 52 34037658
2021 IL-1 family cytokines as drivers and inhibitors of trained immunity. Cytokine 52 34844039
2014 Association between endometriosis and the interleukin 1A (IL1A) locus. Human reproduction (Oxford, England) 52 25336714
2022 The IL-1 family in tumorigenesis and antitumor immunity. Seminars in cancer biology 48 35580824
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