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

• Published in: PloS one Vol. 10; no. 11; p. e0138423
• Main Authors: Takahashi, Kenichiro, Nishida, Atsushi, Shioya, Makoto, Imaeda, Hirotsugu, Bamba, Shigeki, Inatomi, Osamu, Shimizu, Tomoharu, Kitoh, Katsuyuki, Andoh, Akira
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.11.2015; Public Library of Science (PLoS)
• Subjects: Activator protein 1; Blotting, Western; Butadienes - pharmacology; c-Jun protein; Cells, Cultured; Colon - cytology; Cytokines; Enzyme-Linked Immunosorbent Assay; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Flavonoids - pharmacology; Gene expression; Gene Expression - drug effects; Humans; Imidazoles - pharmacology; Immunofluorescence; Immunoglobulins; Inflammation; Inflammatory bowel disease; Interleukin; Interleukin 1; Interleukin-1 - genetics; Interleukin-1 - metabolism; Interleukin-1beta - pharmacology; Intestine; Kinases; MAP kinase; Medicine; Microscopy, Confocal; Molecular modelling; Myofibroblasts - drug effects; Myofibroblasts - metabolism; NF-κB protein; Nitriles - pharmacology; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Proteins; Pyridines - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Rodents; Science; siRNA; Transcription activation; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Transcription Factor RelA - genetics; Transcription Factor RelA - metabolism; Transcription factors; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-α; Variance analysis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0138423

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. 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. 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. 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.