Affinage

IL24

Interleukin-24 · UniProt Q13007

Length
206 aa
Mass
23.8 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-24 (MDA-7) is an IL-10-family cytokine with dual functionality: it acts as a canonical secreted ligand through IL-20R1/IL-20R2 and IL-22R1/IL-20R2 receptor complexes to activate JAK/STAT signaling in epithelial and stromal cells, and it drives cancer-selective apoptosis and toxic autophagy through receptor-independent intracellular mechanisms involving ER stress, ceramide generation, and ROS production (PMID:12811827, PMID:19937735, PMID:20103619). In cancer cells, MDA-7/IL-24 binds the ER chaperone BiP/GRP78 and activates PERK, triggering ceramide elevation via de novo synthesis and acid sphingomyelinase, PP2A-mediated BCL-2 dephosphorylation, translational suppression of Mcl-1 with consequent Bak oligomerization, and p38 MAPK-dependent induction of GADD genes and SARI (PMID:16912197, PMID:20501829, PMID:24282278, PMID:19417161). Secreted IL-24 sustains its own expression through a p38 MAPK-dependent autocrine mRNA stabilization loop acting on the 3′ UTR, inhibits angiogenesis via the IL-22 receptor, downregulates DICER through an ROS/MITF axis, and suppresses tumor cell migration by destabilizing CXCR4 mRNA and inhibiting PI3K/Akt/FAK signaling (PMID:18599461, PMID:20072629, PMID:12941841, PMID:30842276, PMID:25775124). In Th17 cells, IL-24 functions non-canonically by localizing to the inner mitochondrial membrane where it interacts with NDUFA13 (Grim19) to promote mitochondrial STAT3 accumulation, blunting nuclear STAT3 activity and supporting IL-10 production to limit immunopathology (PMID:35819408, PMID:32673565).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 Medium

    Establishing that the mouse IL-24 ortholog (FISP) is a Th2-selective secreted cytokine requiring dual TCR/PKC and STAT6/IL-4R signals resolved the immune-cell context of IL-24 expression before its receptor biology was known.

    Evidence Th1/Th2 differentiation with pharmacological dissection of PKC and STAT6 requirements in mouse T cells

    PMID:11342597

    Open questions at the time
    • Single lab; not replicated with genetic knockouts of PKC isoforms
    • Th2-selectivity was mouse-specific and later complicated by Th17 expression in humans
  2. 2002 Medium

    Demonstrating that adenoviral MDA-7/IL-24 selectively shifts the BAX/BCL-2 ratio and induces G2/M arrest in melanoma but not normal melanocytes established the cancer-selective killing paradigm that dominated subsequent mechanistic dissection.

    Evidence Adenoviral expression in paired normal/cancer melanocyte lines with BCL-2 family protein and cell-cycle analysis

    PMID:11850799

    Open questions at the time
    • Mechanism of cancer selectivity not identified
    • Overexpression system; endogenous IL-24 levels not assessed
  3. 2003 High

    Identifying IL-20R1/IL-20R2 and IL-22R1/IL-20R2 as IL-24 receptors that activate JAK/STAT, while showing cancer-cell killing is JAK/STAT-independent and partially p38 MAPK-dependent, bifurcated the field into canonical signaling versus intracellular death pathways.

    Evidence JAK inhibitors, STAT/JAK-deficient cell lines, p38 MAPK inhibitor, and receptor expression analysis across cancer lines

    PMID:12811827

    Open questions at the time
    • Identity of the intracellular death trigger remained unknown
    • p38 MAPK inhibitor only partially blocked killing, indicating additional pathways
  4. 2003 High

    Secreted MDA-7/IL-24 was shown to inhibit VEGF- and bFGF-driven angiogenesis through the IL-22 receptor, establishing a paracrine antitumor mechanism distinct from direct cancer-cell killing.

    Evidence IL-22R blocking antibody, endothelial differentiation/migration assays, in vivo Matrigel plug and xenograft models

    PMID:12941841

    Open questions at the time
    • Downstream endothelial signaling pathway not delineated
    • Contribution of antiangiogenesis versus direct killing to in vivo efficacy unclear
  5. 2005 High

    Mapping the death-receptor arm showed MDA-7/IL-24 activates c-Jun/ATF2 to transcriptionally induce FasL and Fas, engaging FADD/caspase-8-mediated extrinsic apoptosis in ovarian cancer cells.

    Evidence FasL promoter-reporter, Fas siRNA, FasL blocking antibody, caspase-8 pathway analysis

    PMID:15833826

    Open questions at the time
    • Whether Fas/FasL arm operates in non-ovarian cancers was not tested
    • Upstream trigger linking MDA-7/IL-24 to c-Jun/ATF2 activation not identified
  6. 2006 High

    Identifying BiP/GRP78 as a direct MDA-7/IL-24 binding partner via its C and F helices, with consequent p38 MAPK activation and GADD induction, provided the first molecular explanation for the intracellular ER-stress death pathway.

    Evidence Deletion/point mutagenesis of MDA-7/IL-24, co-immunoprecipitation with BiP/GRP78, subcellular ER localization

    PMID:16912197

    Open questions at the time
    • Structural basis of BiP interaction not resolved at atomic level
    • Whether BiP binding is necessary or sufficient for cancer selectivity not tested with BiP knockdown
  7. 2008 High

    The discovery that secreted MDA-7/IL-24 autocrine-induces its own mRNA through posttranscriptional stabilization (not transcription), sustaining ER stress and ROS, explained the bystander killing phenomenon in untransduced neighboring cancer cells.

    Evidence Promoter activity ruling out transcriptional activation, mRNA stability assays, protein synthesis inhibitor, ER stress and ROS markers

    PMID:18599461

    Open questions at the time
    • RNA-binding protein mediating stabilization not identified
    • Whether autocrine loop operates through the same IL-20R/IL-22R receptors not established
  8. 2008 High

    PERK was established as a required upstream kinase for MDA-7/IL-24-induced autophagy in glioma, linking ER stress to LC3-positive autophagic vacuole formation and subsequent BAX/JNK-mediated mitochondrial apoptosis.

    Evidence PERK−/− cells, ATG5/Beclin-1 siRNA, autophagy inhibitor 3-MA, recombinant GST-MDA-7 treatment

    PMID:18299661

    Open questions at the time
    • Whether PERK activation is direct or secondary to BiP sequestration not resolved
    • Cell-type generality of autophagy-to-apoptosis conversion unclear
  9. 2010 High

    Ceramide was identified as a critical second messenger: MDA-7/IL-24 elevates C16/C24/C24:1 ceramides selectively in cancer cells via de novo synthesis and acid sphingomyelinase, activating PP2A to dephosphorylate BCL-2, while PERK was placed upstream of ceramide generation and ROS production.

    Evidence Ceramide mass spectrometry, myriocin/fumonisin B1 inhibitors, ASMase siRNA, PERK−/− cells, Ca²⁺ and ROS measurement

    PMID:19937735 PMID:20103619

    Open questions at the time
    • Whether ceramide elevation is the primary cancer-selectivity determinant or a downstream amplifier is unclear
    • Role of specific ceramide synthases beyond CerS6 not fully explored
  10. 2010 High

    Translational suppression of Mcl-1 was identified as the key effector of ER stress-mediated apoptosis: MDA-7/IL-24-induced ER stress inhibits Mcl-1 translation, releasing Bak for oligomerization and mitochondrial apoptosis.

    Evidence Forced Mcl-1 expression rescue, Mcl-1 siRNA/knockout sensitization, Mcl-1–Bak co-immunoprecipitation showing dissociation

    PMID:20501829

    Open questions at the time
    • Whether Mcl-1 translational suppression is eIF2α-phosphorylation-dependent was inferred but not directly tested with eIF2α mutants
  11. 2010 High

    p38 MAPK was shown to stabilize IL-24 mRNA via its 3′ UTR, providing the molecular basis for the autocrine amplification loop and positioning p38 MAPK as both a downstream effector and a feed-forward stabilizer of IL-24 expression.

    Evidence Tet-off 3′ UTR reporter, p38 MAPK inhibitor SB202190, constitutively active MKK6

    PMID:20072629

    Open questions at the time
    • The specific RNA-binding protein(s) that p38 MAPK regulates to stabilize IL-24 mRNA remain unidentified
    • Whether this loop operates in immune cells in addition to cancer cells is unknown
  12. 2009 High

    Ceramide-dependent CD95 (Fas) clustering at the plasma membrane was linked to MDA-7/IL-24 action in renal carcinoma, unifying the ceramide and death-receptor pathways: ASMase/CerS6-generated ceramide causes CD95 aggregation and procaspase-8 recruitment, upstream of PERK-dependent JNK/p38 signaling.

    Evidence CD95 clustering assay, ASMase/CerS6 siRNA, PERK dominant-negative and knockout, co-IP of CD95 with procaspase-8

    PMID:19417161

    Open questions at the time
    • Whether CD95 clustering is a general feature across cancer types or renal-carcinoma-specific
    • Temporal ordering of ceramide versus PERK activation not fully resolved
  13. 2013 High

    SARI (suppressor of AP-1) was identified as a necessary downstream effector of MDA-7/IL-24's antitumor activity, induced through receptor-mediated p38 MAPK signaling, connecting the extracellular signaling arm to intracellular tumor suppression.

    Evidence SARI antisense abolishing MDA-7/IL-24 killing, p38 MAPK inhibitor, recombinant His-MDA-7 acting through IL-20R/IL-22R receptors

    PMID:24282278

    Open questions at the time
    • SARI's direct transcriptional targets mediating apoptosis not defined
    • Whether SARI is required in all cancer types not tested
  14. 2015 High

    IL-24 was shown to post-transcriptionally destabilize CXCR4 mRNA, reducing its half-life by >40%, thereby suppressing AKT/mTOR/HIF-1α signaling and cancer cell migration — extending IL-24's anti-invasion mechanism beyond FAK/MMP suppression.

    Evidence Doxycycline-inducible IL-24, CXCR4 mRNA half-life measurement, CXCR4 siRNA, migration/invasion assays

    PMID:25775124

    Open questions at the time
    • The RNA-destabilizing mechanism (e.g., specific RBP or miRNA involved) not identified
    • Whether CXCR4 mRNA destabilization occurs in non-lung cancer contexts unknown
  15. 2019 High

    MDA-7/IL-24 was found to downregulate DICER through receptor-dependent ROS production and MITF suppression, cancer-selectively impairing miRNA biogenesis (e.g., reducing mature miR-221); DICER overexpression rescued cancer cells, establishing a novel effector arm.

    Evidence DICER gain/loss-of-function, MITF manipulation, ROS measurement, northern blot for miRNA intermediates, in vivo xenograft rescue

    PMID:30842276

    Open questions at the time
    • Which DICER-dependent miRNAs beyond miR-221 are functionally important not mapped
    • How MITF downregulation specifically targets DICER transcription not resolved
  16. 2020 High

    In Th17 cells, IL-17A-induced NF-κB was shown to drive autocrine IL-24 expression, which in turn represses the pathogenic Th17 program (GM-CSF, IL-17F) and ameliorates autoimmune uveitis, establishing IL-24 as an intrinsic negative-feedback cytokine in Th17 biology.

    Evidence NF-κB signaling dissection, IL-24 silencing in Th17 cells, in vivo EAU model with IL-24 treatment/silencing, human Th17 validation

    PMID:32673565

    Open questions at the time
    • Whether IL-24 represses GM-CSF/IL-17F transcriptionally or post-transcriptionally not resolved
    • Receptor dependence versus intracellular action in Th17 regulation not distinguished in this study
  17. 2020 High

    IL-24 was shown to synergize with IL-4 to promote M2 macrophage polarization by suppressing SOCS1/SOCS3, enhancing STAT6/PPARγ, and IL-24 deficiency attenuated pulmonary fibrosis, revealing a pro-fibrotic immunomodulatory role distinct from its antitumor function.

    Evidence IL-24 knockout mice, SOCS1/3 and STAT6/PPARγ signaling analysis, bleomycin-induced fibrosis model

    PMID:33144678

    Open questions at the time
    • Whether IL-24 acts directly on macrophages or indirectly through other cell types not fully resolved
    • Receptor complex mediating IL-24's effect on macrophages not identified
  18. 2022 High

    The discovery that IL-24 localizes to the inner mitochondrial membrane and interacts with NDUFA13/Grim19 to promote mitochondrial STAT3 accumulation — independently of its cell-surface receptors — established a non-canonical cell-intrinsic mechanism by which IL-24 supports IL-10 production in Th17 cells and limits autoimmune pathology.

    Evidence Subcellular fractionation, co-immunoprecipitation with Grim19, receptor-independent functional assays, mitochondrial STAT3 measurement, EAE model

    PMID:35819408

    Open questions at the time
    • How IL-24 is imported into the inner mitochondrial membrane is unknown
    • Whether mitochondrial IL-24 function extends to other immune or non-immune cell types not tested
    • Structural basis of IL-24–Grim19 interaction not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular basis of cancer selectivity — why intracellular MDA-7/IL-24 triggers ER stress and apoptosis in tumor cells but not normal cells — remains mechanistically unresolved despite extensive downstream pathway characterization.
  • No cancer-cell-specific factor or threshold mechanism identified
  • How mitochondrial and ER-stress functions relate to each other in immune cells is unexplored
  • No structural model of IL-24 in complex with BiP, Grim19, or receptors exists

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
Localization
GO:0005576 extracellular region 4 GO:0005783 endoplasmic reticulum 3 GO:0005739 mitochondrion 1
Pathway
R-HSA-5357801 Programmed Cell Death 9 R-HSA-162582 Signal Transduction 6 R-HSA-8953854 Metabolism of RNA 4 R-HSA-9612973 Autophagy 4 R-HSA-168256 Immune System 3
Partners
BECN1CLUHSPA5IL20RAIL20RBIL22RA1NDUFA13

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 MDA-7/IL-24 protein binds to IL-20R1/IL-20R2 and IL-22R1/IL-20R2 receptor complexes on the cell surface, activating JAK/STAT signaling pathways (STAT1 and STAT3); however, cancer-specific apoptosis induction occurs through JAK/STAT-independent pathways, as JAK inhibitors (AG490), tyrosine kinase inhibitors, and STAT/JAK-deficient cells do not abrogate Ad.mda-7-induced apoptosis, whereas p38 MAPK inhibitor (SB203580) partially blocks killing. Pharmacological inhibitors of JAK/STAT pathway, STAT/JAK-deficient cell lines, receptor expression analysis, apoptosis assays Journal of cellular physiology High 12811827
2003 Secreted MDA-7/IL-24 inhibits angiogenesis (endothelial cell differentiation and migration induced by VEGF and bFGF) through the IL-22 receptor; blocking antibody to IL-22 receptor abrogates this antiangiogenic activity in vitro and reduces tumor vascularization in vivo. In vitro endothelial differentiation/migration assays, blocking antibody, in vivo Matrigel plug assay, xenograft model with stable sMDA-7/IL-24-expressing cells Cancer research High 12941841
2006 MDA-7/IL-24 physically interacts with the ER chaperone BiP/GRP78 through its C and F helices (identified by deletion and mutational analysis), localizes to the endoplasmic reticulum, and activates p38 MAPK and GADD gene expression, culminating in cancer-selective apoptosis. Deletion analysis, rationally designed mutagenesis, co-immunoprecipitation/physical interaction assay, subcellular localization, downstream signaling measurement Cancer research High 16912197
2005 Ad.mda-7-induced apoptosis in human ovarian cancer cells involves activation of transcription factors c-Jun and ATF2, which stimulate transcription of FasL and Fas; subsequent activation of NF-κB, FADD, FAF1, and caspase-8 mediates cell death. Inhibition of Fas by siRNA or FasL by blocking antibody significantly reduces apoptosis. Promoter-reporter gene analysis, siRNA knockdown of Fas, FasL blocking antibody (NOK-1), western blot for pathway components Cancer research High 15833826
2008 Secreted MDA-7/IL-24 protein induces autocrine upregulation of endogenous mda-7/IL-24 mRNA through posttranscriptional stabilization (not promoter activation), dependent on de novo protein synthesis; this autocrine loop sustains ER stress (BiP/GRP78, GRP94, GADD153, phospho-eIF2α) and ROS production, mediating cancer-specific bystander killing. Promoter activity assay (ruling out transcriptional activation), mRNA stability assay, protein synthesis inhibitor, ER stress marker measurement, ROS detection Proceedings of the National Academy of Sciences of the United States of America High 18599461
2010 MDA-7/IL-24-induced ER stress in prostate cancer cells causes apoptosis through translational inhibition of the anti-apoptotic protein Mcl-1; forced Mcl-1 expression blocks mda-7/IL-24 lethality, while Mcl-1 knockdown/knockout sensitizes cells. Mcl-1 downregulation relieves its association with Bak, causing Bak oligomerization and cell death. Forced expression of Mcl-1, siRNA/gene knockout of Mcl-1, co-immunoprecipitation of Mcl-1 with Bak, cell death assays Cancer research High 20501829
2010 MDA-7/IL-24 induces cancer-specific apoptosis through a ceramide-mediated ER stress pathway: Ad.mda-7 selectively elevates ceramides (C16, C24, C24:1) in prostate cancer but not normal cells via de novo synthesis (serine palmitoyltransferase) and acid sphingomyelinase; ceramide activates PP2A leading to BCL-2 dephosphorylation; ceramide inhibition blocks ER stress markers (BiP/GRP78, GADD153, phospho-eIF2α). Ceramide mass spectrometry, pharmacological inhibitors (myriocin/ISP1, fumonisin B1), siRNA knockdown of ASMase, PP2A activity assay, ER stress marker measurement Journal of cellular physiology High 19937735
2010 PERK (protein kinase R-like ER kinase) activation is required for MDA-7/IL-24-induced ceramide generation and subsequent Ca2+ elevation and ROS production in glioma cells; PERK inhibition blocks ceramide/dihydroceramide generation, and ROS mediate autophagy and cell death. Ceramide synthase 6 (CerS6) and thioredoxin (TRX) are key downstream regulators. PERK inhibition/knockout (PERK-/- cells), ceramide measurement, Ca2+ measurement, ROS measurement, autophagy assay, orthotopic tumor model Cancer research High 20103619
2003 Ad.mda-7 (MDA-7/IL-24) radiosensitizes glioma cells through JNK1/2 activation; inhibition of JNK1/2 (but not p38) abolishes radiosensitization, while Ad.mda-7 enhances p38 and ERK1/2 activity in non-irradiated cells. Pharmacological kinase inhibitors, colony formation/MTT assays, cell cycle analysis, kinase activity measurement Cancer biology & therapy Medium 14508103
2004 MDA-7/IL-24 inhibits lung cancer cell migration and invasion by downregulating PI3K/Akt, focal adhesion kinase (FAK), and matrix metalloproteinases MMP-2 and MMP-9. Adenoviral overexpression, migration/invasion assays (Boyden chamber), western blot for pathway proteins, in vivo experimental metastasis model Molecular therapy Medium 15093181
2008 GST-MDA-7 (recombinant MDA-7/IL-24 protein) induces PERK-dependent autophagy in glioma cells; PERK activation drives formation of LC3-positive autophagic vacuoles (suppressed by ATG5/Beclin-1 knockdown or HSP70/BiP overexpression) that is causal in triggering mitochondrial apoptosis through JNK1-3 and BAX. PERK-/- cells, ATG5/Beclin-1 siRNA, autophagy inhibitors (3-methyladenine), LC3 immunofluorescence, co-immunoprecipitation, cell death assays Autophagy High 18299661
2009 In renal carcinoma cells, recombinant MDA-7/IL-24 (GST-MDA-7) induces ceramide-dependent clustering of CD95 (Fas) at the plasma membrane, association of CD95 with procaspase-8, and subsequent PERK-dependent ER stress; CD95 clustering is blocked by knockdown of acid sphingomyelinase or ceramide synthase-6, and PERK knockout abolishes JNK/p38 signaling and cell death. CD95 clustering assay, co-immunoprecipitation of CD95 with procaspase-8, caspase-8 inhibitor, siRNA knockdown of ASMase/CerS6/CD95, PERK dominant-negative and knockout, autophagy (LC3) assay Molecular cancer therapeutics High 19417161
2013 MDA-7/IL-24 induces expression of SARI (suppressor of AP-1, induced by IFN) in cancer cells through p38 MAPK phosphorylation leading to GADD gene transcription; SARI expression is necessary for mda-7/IL-24 antitumor effects, as SARI antisense abolishes killing. Secreted MDA-7/IL-24 binds IL-20R1/IL-20R2 or IL-22R/IL-20R2 receptors to activate p38 MAPK and induce SARI. Antisense inhibition of SARI, p38 MAPK inhibitor, receptor binding, western blot for SARI/GADD, recombinant His-MDA-7 protein treatment Cancer research High 24282278
2012 MDA-7/IL-24 interacts with the pro-autophagic protein Beclin-1 in leukemia cells (co-immunoprecipitation), and mda-7/IL-24-induced autophagy is mediated through the class III PI3K/Beclin-1 complex; this autophagy promotes cancer cell survival, and its inhibition (wortmannin) enhances mda-7/IL-24-induced cell death. Co-immunoprecipitation of MDA-7/IL-24 with Beclin-1, immunofluorescence, autophagy inhibitors (wortmannin), ATG5/Beclin-1 knockdown, xenograft model Cancer gene therapy Medium 19730452
2012 Clusterin (CLU) is identified as an MDA-7/IL-24-interacting protein in prostate cancer cells; MDA-7/IL-24 decreases soluble CLU (sCLU) and increases nuclear CLU (nCLU), with early sCLU increase creating a cytoprotective effect. In sCLU-overexpressing cancer cells, MDA-7/IL-24 converts sCLU to nCLU causing G2/M arrest and apoptosis. Co-immunoprecipitation identifying CLU as MDA-7/IL-24 binding partner, stable cell lines overexpressing sCLU, western blot for sCLU/nCLU, cell cycle analysis, xenograft model Journal of cellular physiology Medium 21732348
2010 p38 MAPK stabilizes IL-24 mRNA by acting on the 3' UTR; p38 MAPK inhibitor (SB202190) accelerates IL-24 mRNA decay, and a constitutively active MKK6 mutant (which selectively activates p38 MAPK) reduces mRNA degradation mediated by the IL-24 3' UTR in a reporter construct. mRNA stability assay, p38 MAPK inhibitor, constitutively active MKK6 overexpression, tet-off 3' UTR reporter construct PloS one High 20072629
2012 miR-203 directly targets IL24 mRNA in keratinocytes, providing posttranscriptional repression; validated by miR-203 overexpression, inhibition, and mutagenesis of the target site in primary keratinocytes and cell lines. miRNA overexpression/inhibition, mutagenesis of miR-203 binding site in IL24 3' UTR, quantitative RT-PCR, primary keratinocyte experiments Cytokine High 22917968
2008 MDA-7/IL-24 in melanoma cells induces secretion of endogenous IFN-β (class I IFN), which leads to upregulation of IRF-2 (competing with IRF-1), downregulation of iNOS, and activation of TRAIL and Fas-FasL apoptotic cascades. ELISA for IFN-β secretion, IRF-1/IRF-2 expression analysis, TRAIL/FasL measurement, apoptosis assays in melanoma cell lines Cytokine Medium 18511292
2002 Adenovirus-expressed MDA-7/IL-24 selectively increases the ratio of pro-apoptotic (BAX, BAK) to anti-apoptotic (BCL-2, BCL-XL) proteins in melanoma cells, causes G2/M cell cycle arrest, and leads to secretion of MDA-7 protein; normal melanocytes do not undergo apoptosis. Adenoviral gene transfer, western blot for BCL-2 family proteins, cell cycle analysis (flow cytometry), ELISA for secreted protein, normal vs. cancer cell comparison Oncogene Medium 11850799
2020 IL-17A binding to its receptor on Th17 cells activates NF-κB, which induces IL-24 expression in an autocrine loop; IL-24 in turn represses the Th17 cytokine program (GM-CSF, IL-17F) and in vivo treatment with IL-24 ameliorates autoimmune uveitis (EAU), while IL-24 silencing in Th17 cells enhances disease. In vitro mechanistic studies of NF-κB activation and IL-24 induction, IL-24 silencing in Th17 cells, in vivo EAU model with IL-24 treatment/silencing, human Th17 cell validation Immunity High 32673565
2022 In Th17 cells, IL-24 acts cell-intrinsically and independently of its cell-surface receptor to promote IL-10 secretion; IL-24 is recruited to the inner mitochondrial membrane where it interacts with NADH dehydrogenase subunit Grim19 (NDUFA13, complex I), and together Grim19 and IL-24 promote accumulation of STAT3 in the mitochondrial compartment, acting as a rheostat to blunt nuclear STAT3 activity and support robust IL-10 responses. Subcellular fractionation/localization of IL-24 to mitochondria, co-immunoprecipitation with Grim19, receptor-independent functional studies, mitochondrial STAT3 accumulation measurement, EAE model The Journal of experimental medicine High 35819408
2020 IL-24 synergizes with IL-4 to promote M2 macrophage polarization by suppressing IL-4-induced expression of SOCS1 and SOCS3, thereby enhancing STAT6/PPARγ signaling; IL-24 deficiency attenuates TGF-β1 production and M2 macrophage infiltration in bleomycin-induced pulmonary fibrosis. IL-24 knockout mice, SOCS1/SOCS3 expression analysis, STAT6/PPARγ signaling measurement, M2 macrophage quantification, BLM-induced fibrosis model Cell death and differentiation High 33144678
2015 IL-24 post-transcriptionally regulates CXCR4 mRNA by decreasing its half-life (>40%), thereby reducing CXCR4 protein and downstream signaling (pAKT, pmTOR, pPRAS40, HIF-1α), and inhibiting lung cancer cell migration and invasion; this is shown using doxycycline-inducible IL-24 expression, CXCR4 siRNA, and combination with CXCR4 antagonists. Doxycycline-inducible stable IL-24 expression, CXCR4 mRNA stability assay (half-life measurement), western blot for downstream targets, migration/invasion assays, CXCR4 siRNA, luciferase reporter PloS one High 25775124
2019 MDA-7/IL-24 downregulates DICER (miRNA processing enzyme) in cancer cells but not normal cells, through canonical IL-20/IL-22 receptors; downregulation is ROS-dependent and mediated through the melanogenesis-associated transcription factor MITF. DICER downregulation reduces mature miR-221 (without affecting pri-miR-221) and contributes to cancer cell death; DICER overexpression rescues cells from MDA-7/IL-24-induced death. Gain/loss-of-function for DICER, MITF, and receptor manipulation; ROS measurement; northern/qPCR for miRNA biogenesis intermediates; stable DICER-overexpressing cell lines; in vivo xenograft with stable DICER cells Proceedings of the National Academy of Sciences of the United States of America High 30842276
2011 Pharmacological inhibition of Mcl-1 with Sabutoclax (BI-97C1) sensitizes prostate cancer cells to MDA-7/IL-24-induced apoptosis; the combination causes autophagy that facilitates NOXA- and Bim-induced, Bak/Bax-mediated mitochondrial apoptosis; ABT-737 (which does not inhibit Mcl-1) does not sensitize cells, confirming Mcl-1 specificity. Pharmacological Mcl-1 inhibition, autophagy assay, NOXA/Bim/Bak/Bax assessment, xenograft and transgenic mouse models (Hi-myc), TUNEL/Ki-67 staining Proceedings of the National Academy of Sciences of the United States of America High 21555592
2017 ZBTB7A transcriptionally represses LINC00473 by directly binding its promoter; LINC00473 interacts with transcription factor C/EBPβ, facilitating C/EBPβ binding to the IL24 promoter and promoting IL24 transcription. Loss of ZBTB7A reduces IL24 expression and increases cisplatin resistance in osteosarcoma. ChIP assay (ZBTB7A binding to LINC00473 promoter), RNA-protein interaction (LINC00473-C/EBPβ), C/EBPβ ChIP at IL24 promoter, loss/gain-of-function experiments Neoplasia Medium 28942243
2010 IL-24 inhibits TGFα-induced proliferation and migration of normal human epidermal keratinocytes (NHEKs) in vitro; IL-24 is expressed in keratinocytes during wound repair with maximum expression at days 2-6 post-wounding, induced by TGFα, TGFβ, IFNγ, and IFNβ. Immunohistochemistry of wound tissues, in vitro wound repair assay, migration assay, cytokine stimulation, western blot Experimental dermatology Medium 20545760
2013 IL-24 produced by mast cells (induced by T cell-derived microvesicles) activates keratinocyte STAT3 phosphorylation in vitro, establishing a functional signaling link between MC-derived IL-24 and keratinocyte activation. Co-culture of mast cells with microvesicles, ELISA for IL-24 protein, STAT3 phosphorylation assay in keratinocytes treated with MC-conditioned medium, immunohistochemistry of psoriatic lesions The Journal of allergy and clinical immunology Medium 23768573
2008 IL-24 induces apoptosis of IL-2-activated (cycling) CLL B cells through dephosphorylation of STAT3 (via activation of tyrosine phosphatase PTP1B) and concomitant stabilization and phosphorylation of p53; blocking phospho-STAT3 (a transcriptional repressor of p53) relieves repression of p53, which then drives apoptosis via caspase pathway. Sequential cytokine treatment (IL-2 then IL-24), phospho-STAT3 western blot, pervanadate (phosphatase inhibitor) reversal, p53 transcription/protein/phosphorylation assay, pifithrin-α (p53 inhibitor) rescue, caspase inhibitor rescue Journal of immunology Medium 18941194
2006 IL-19, IL-20, and IL-24 signal through two heterodimeric receptor complexes: IL-20R1/IL-20R2 and IL-22R1/IL-20R2; both complexes are expressed on keratinocytes (IL-22R1 at 10-fold higher levels than IL-20R1), while immune cells lack these receptor chains and do not activate STAT molecules in response to these cytokines. IFN-γ further increases IL-22R1 and decreases IL-20R1 expression on keratinocytes. Quantitative receptor expression analysis (qPCR), STAT activation assay in immune cells and keratinocytes, cytokine stimulation experiments Experimental dermatology Medium 17083366
2001 The mouse ortholog of IL-24 (FISP, IL-4-induced secreted protein) is selectively expressed and secreted by Th2 cells; its expression requires two signals: TCR signaling involving protein kinase C activation and STAT6-dependent IL-4R signaling. Th1/Th2 differentiation assays, pharmacological inhibition of PKC, IL-4R blocking, STAT6 requirement analysis, protein secretion assay Journal of immunology Medium 11342597
2020 IL-24 promotes epithelial-mesenchymal transition (EMT) in bronchial epithelial cells via STAT3 and ERK1/2 signaling pathways (upregulating vimentin and α-SMA, downregulating E-cadherin); IL-37 reverses IL-24-induced EMT by blocking ERK1/2 and STAT3, and in vivo IL-24 silencing or IL-37 treatment reverses EMT biomarker expression in an HDM-induced asthma model. BEAS-2B cell stimulation with IL-24, EMT biomarker (E-cadherin, vimentin, α-SMA) assay, wound healing/Transwell migration, STAT3/ERK1/2 phosphorylation assay, siRNA-IL-24 in vivo in murine asthma model Respiratory research Medium 36100847

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29. The Journal of allergy and clinical immunology 256 18405958
2006 Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs. Experimental dermatology 204 17083366
2002 The cancer growth suppressing gene mda-7 induces apoptosis selectively in human melanoma cells. Oncogene 180 11850799
2005 Is mda-7/IL-24 a "magic bullet" for cancer? Cancer research 179 16287994
2003 Melanoma differentiation-associated gene 7/interleukin (IL)-24 is a novel ligand that regulates angiogenesis via the IL-22 receptor. Cancer research 163 12941841
2006 mda-7/IL-24: multifunctional cancer-specific apoptosis-inducing cytokine. Pharmacology & therapeutics 160 16464504
2020 The Cytokine IL-17A Limits Th17 Pathogenicity via a Negative Feedback Loop Driven by Autocrine Induction of IL-24. Immunity 149 32673565
2003 mda-7/IL-24, a novel cancer selective apoptosis inducing cytokine gene: from the laboratory into the clinic. Cancer biology & therapy 145 14508078
2003 MDA-7/IL-24: novel cancer growth suppressing and apoptosis inducing cytokine. Cytokine & growth factor reviews 143 12485618
2002 Loss of MDA-7 expression with progression of melanoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 123 11844832
2020 IL-24 deficiency protects mice against bleomycin-induced pulmonary fibrosis by repressing IL-4-induced M2 program in macrophages. Cell death and differentiation 121 33144678
2008 Autocrine regulation of mda-7/IL-24 mediates cancer-specific apoptosis. Proceedings of the National Academy of Sciences of the United States of America 114 18599461
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