Interleukin (IL)-1β Is a Strong Inducer of IL-36. Expression in Human Colonic Myofibroblasts

Backgrounds and aims Interleukin (IL)-36 cytokines are members of the IL-1 cytokine family. In this study, we investigated the expression of IL-36 gamma in human colonic myofibroblasts to explore the molecular mechanisms underlying IL-36 gamma induction. Materials and methods IL-36 mRNA was analyzed by real-time PCR method. Secretion of IL-36 gamma protein was evaluated by Western blot and ELISA analyses. Molecular mechanism of IL-36 gamma induction was evaluated by siRNA analyses and immunofluorescence experiments. Results IL-36 gamma mRNA expression was scarcely detected in the cells without stimulation. IL-1 beta induced a marked increase of IL-36 gamma mRNA expression. TNF-alpha markedly enhanced IL-1 beta-induced IL36 gamma mRNA expression. These responses were confirmed at the protein levels. The inhibitors for ERK1/2 (PD98059 and U0216) and a p38 MAPK (SB203580) significantly reduced the IL1 beta- induced IL-36 gamma mRNA expression. In addition, the siRNAs specific for NF-kappa B p65 andAP1 (c-Jun) significantly reduced the expression of IL-1 beta-induced IL-36 gamma mRNA. Conclusions Colonic myofibroblasts are cellular source of IL-36 gamma in the intestine. IL-36 gamma expression was induced by the combination of IL-1 beta and TNF-alpha via activation of MAPKs and transcription factors, NF-kappa B and AP-1.