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

PLoS One

Makoto Shioya¹  Hirotsugu Imaeda¹  Katsuyuki Kitoh¹  Akira Andoh¹  Atsushi Nishida¹  Osamu Inatomi¹  Kenichiro Takahashi¹  Shigeki Bamba¹  Tomoharu Shimizu² 

[1] Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520–2192, Japan;Department of Surgery, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520–2192, Japan

关键词: Transcription factors;    Colon;    Fibroblasts;    Cytokines;    Small interfering RNAs;    Inflammatory bowel disease;    Messenger RNA;    Gastrointestinal tract;   

DOI  :  10.1371/journal.pone.0138423

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Backgrounds and aims Interleukin (IL)-36 cytokines are members of the IL-1 cytokine family. In this study, we investigated the expression of IL-36γ in human colonic myofibroblasts to explore the molecular mechanisms underlying IL-36γ induction. Materials and methods IL-36 mRNA was analyzed by real-time PCR method. Secretion of IL-36γ protein was evaluated by Western blot and ELISA analyses. Molecular mechanism of IL-36γ induction was evaluated by siRNA analyses and immunofluorescence experiments. Results IL-36γ mRNA expression was scarcely detected in the cells without stimulation. IL-1β induced a marked increase of IL-36γ mRNA expression. TNF-α markedly enhanced IL-1β-induced IL-36γ 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 IL-1β-induced IL-36γ mRNA expression. In addition, the siRNAs specific for NF-κB p65 and AP-1 (c-Jun) significantly reduced the expression of IL-1β-induced IL-36γ mRNA. Conclusions Colonic myofibroblasts are cellular source of IL-36γ in the intestine. IL-36γ expression was induced by the combination of IL-1β and TNF-α via activation of MAPKs and transcription factors, NF-κB and AP-1.

【 授权许可】

CC BY