Interleukin-36 Induces the Inflammatory Mediators from Human Colonic Subepithelial Myofibroblasts

Background: Interleukin (IL) -36 is a new member of IL-1 family. It has been reported that IL-36 was associated with chronic inflammatory disorders, such as psoriasis and rheumatoid arthritis. There are few reports about the role of IL-36 in intestinal inflammation, including inflammatory bowel disease (IBD). In the present study, we investigated IL-36 expression in the inflamed mucosa of patients with IBD and characterized biological activities of IL-36 in human colonic subepithelial myofibroblasts (SEMFs). Methods: SEMFs were stimulated with IL-36 cytokines. The expression of mRNA and protein in the samples were analyzed by real-time PCR and ELISA, respectively. Western blots were performed to evaluate the signal transduction of IL-36. Results: IL-36γ mRNA expression significantly increased in active UC samples as compared to in healthy and inactive UC samples. IL-36α and IL-36γ, but not IL-36β, significantly enhanced the secretion of inflammatory mediators from SEMFs. The inductions of these mediators by IL-36α and IL-36γ were mediated by mitogen activated protein kinases (MAPKs), leading to the activation of nucleic factor kappa-B (NFκB). Conclusions: IL-36α and IL-36γ induced inflammatory mediators in SEMFs through the activation of MAPKs and NFκB. We suggest that IL-36 plays an important role in intestinal inflammation and may contribute to the pathophysiology of IBD.