title: Interleukin-32α expression in human colonic subepithelial myofibroblasts.
abstract: Interleukin (IL)-32 is a recently described proinflammatory cytokine, characterized by induction of nuclear factor (NF)-κB activation. We studied IL-32α expression in human colonic subepithelial myofibroblasts (SEMFs). Colonic SEMFs were isolated from normal human colon tissue. IL-32α protein expression was evaluated by Western blot analyses, and IL-32α mRNA expression was analyzed by real-time PCR. IL-32α mRNA was weakly expressed without a stimulus, and its expression was markedly enhanced by IL-1ß and TNF-α. IL-1ß and TNF-α enhanced intracellular accumulation of IL-32α protein, but IL-32α was not detected in supernatants. Each cytokine dose- and time-dependently induced IL-32α mRNA expression. An inhibitor of phosphatidylinositol 3-kinase (LY294002) significantly suppressed IL-1ß- and TNF-α-induced IL-32α mRNA expression, although MAPK inhibitors had no effect. Akt activation in response to these cytokines was confirmed by Western blotting. Blockade of NF-κB activation by an adenovirus expressing a stable mutant form of IκBα markedly suppressed IL-1ß- and TNF-α-induced IL-32α mRNA expression. Human colonic SEMFs expressed IL-32α in response to IL-1ß and TNF-α. IL-32α mRNA expression depends on the phosphatidylinositol 3-kinase and the NF-κB system.
authors.affiliation: Department of Medicine, Graduate School of Medicine, Shiga University of Medical Science, Seta Tukinowa, Otsu, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Yagi
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Imaeda
authors.forename: Tomoki
authors.initials: T
authors.lastname: Aomatsu
authors.forename: Rie
authors.initials: R
authors.lastname: Ohsaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Inatomi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Bamba
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tsujikawa
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujiyama
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; C496971:IL32 protein, human; D053583:Interleukin-1beta; D007378:Interleukins; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases