title: Interleukin (IL)-1β Is a Strong Inducer of IL-36γ Expression in Human Colonic Myofibroblasts.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishida
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shioya
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Imaeda
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Bamba
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Inatomi
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kitoh
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
mesh_terms: D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D018613:Microscopy, Confocal; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002070:Butadienes; D005419:Flavonoids; C508589:IL36G protein, human; D007093:Imidazoles; D007375:Interleukin-1; D053583:Interleukin-1beta; D009570:Nitriles; D011725:Pyridines; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one