ArticleThe Journal of biological chemistry2020
Inflammatory and mitogenic signals drive interleukin 23 subunit alpha (IL23A) secretion independent of IL12B in intestinal epithelial cells.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Role of PANoptosis in intestinal diseases and its therapeutic implications.Journal of molecular medicine (Berlin, Germany) · 2026Review
- A Literature Review of Interleukins in the Development and Treatment of Breast Cancer.International journal of molecular sciences · 2026Review
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- IL-12 and IL-23 pathway inhibition in inflammatory bowel disease.Nature reviews. Gastroenterology & hepatology · 2023Review
- The Role of IL-23 in the Pathogenesis and Therapy of Inflammatory Bowel Disease.International journal of molecular sciences · 2023Review
- Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice.Microbiome · 2023Article
- Successful treatment with MEK-inhibitor in a patient with NRAS-related cutaneous skeletal hypophosphatemia syndrome.Genes, chromosomes & cancer · 2022Article
- Exposure to e-cigarette vapor extract induces vocal fold epithelial injury and triggers intense mucosal remodeling.Disease models & mechanisms · 2022Article
- The Role of Inflammatory Cytokines in the Pathogenesis of Colorectal Carcinoma-Recent Findings and Review.Biomedicines · 2022Review
- Introducing New Potential Biomarkers for Celiac Disease among the Genes Extracted from General Databases.Middle East journal of digestive diseases · 2022Article
- Nanoparticles Carrying NF-κB p65-Specific siRNA Alleviate Colitis in Mice by Attenuating NF-κB-Related Protein Expression and Pro-Inflammatory Cellular Mediator Secretion.Pharmaceutics · 2022Article
- Systemic Interleukins' Profile in Early and Advanced Colorectal Cancer.International journal of molecular sciences · 2021Review
- Crossing the boundaries: IL-23 and its role in linking inflammation of the skin, gut and joints.Rheumatology (Oxford, England) · 2021Article
- Low-intensity ultrasound inhibits melanoma cell proliferation in vitro and tumor growth in vivo.Journal of medical ultrasonics (2001) · 2021Article
- Role of NKG2a/ciScience · 2021Article
- Shiga toxin remodels the intestinal epithelial transcriptional response to Enterohemorrhagic Escherichia coli.PLoS pathogens · 2021Article
- An Integrative Network Approach to Identify Common Genes for the Therapeutics in Tuberculosis and Its Overlapping Non-Communicable Diseases.Frontiers in pharmacology · 2021Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The heterodimeric cytokine interleukin-23 (IL-23 or IL23A/IL12B) is produced by dendritic cells and macrophages and promotes the proinflammatory and regenerative activities of T helper 17 (Th17) and innate lymphoid cells. A recent study has reported that IL-23 is also secreted by lung adenoma cells and generates an inflammatory and immune-suppressed stroma. Here, we observed that proinflammatory tumor necrosis factor (TNF)/NF-κB and mitogen-activated protein kinase (MAPK) signaling strongly induce IL23A expression in intestinal epithelial cells. Moreover, we identified a strong crosstalk between the NF-κB and MAPK/ERK kinase (MEK) pathways, involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto-oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), and RUNX3. Collectively, these proteins induced IL23A secretion, confirmed by immunoprecipitation of endogenous IL23A from activated human colorectal cancer (CRC) cell culture supernatants. Interestingly, IL23A was likely secreted in a noncanonical form, as it was not detected by an ELISA specific for heterodimeric IL-23 likely because IL12B expression is absent in CRC cells. Given recent evidence that IL23A promotes tumor formation, we evaluated the efficacy of MAPK/NF-κB inhibitors in attenuating IL23A expression and found that the MEK inhibitor trametinib and BAY 11-7082 (an IKKα/IκB inhibitor) effectively inhibited IL23A in a subset of human CRC lines with mutant KRAS or BRAFV600E mutations. Together, these results indicate that proinflammatory and mitogenic signals dynamically regulate IL23A in epithelial cells. They further reveal its secretion in a noncanonical form independent of IL12B and that small-molecule inhibitors can attenuate IL23A secretion.
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