title: Expression of interleukin-24 and its receptor in human pancreatic myofibroblasts.
abstract: Interleukin (IL)-24 is a member of the IL-10 family of cytokines. In this study, we investigated IL-24 expression in chronic pancreatitis tissue and characterized the molecular mechanisms responsible for IL-24 expression in human pancreatic myofibroblasts. IL-24 expression in the tissues was evaluated by immunohistochemical methods. IL-24 mRNA and protein expression in the pancreatic myofibroblasts was determined by real-time-PCR and ELISA, respectively. IL-24 was expressed by α-smooth muscle actin-positive myofibroblasts in the chronic pancreatitis tissues. In isolated human pancreatic myofibroblasts, IL-1β significantly enhanced IL-24 mRNA and protein expression. The p38 MAPK inhibitor SB203580 and the PI3K inhibitor LY294002 significantly reduced the IL-β-induced IL-24 mRNA expression. An adenovirus containing a dominant-negative mutant of c-Jun significantly inhibited the effects of IL-1β on IL-24 mRNA expression, indicating that the IL-1β-induced IL-24 mRNA expression was mediated by the activation of transcription factor AP-1. Pancreatic myofibroblasts expressed IL-22R1, IL-20R1 and IL-20R2, and recombinant IL-24 induced the phosphorylation of p42/44, p38, JNK and STAT1/3. IL-24 is expressed in chronic pancreatitis tissue, and may play a role in the pathophysiology of chronic pancreatitis via autocrine pathways.
authors.affiliation: Department of Medicine, Graduate School of Medicine, Shiga University                     of Medical Science, Seta Tsukinowa, Otsu, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Imaeda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishida
authors.forename: Osamu
authors.initials: O
authors.lastname: Inatomi
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujiyama
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D058628:Myofibroblasts / Q000166:cytology / Q000378:metabolism*; D050500:Pancreatitis, Chronic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000099180:Interleukin-24
chemical_list: D053583:Interleukin-1beta; D007378:Interleukins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D018808:Transcription Factor AP-1; D048051:p38 Mitogen-Activated Protein Kinases; D000099180:Interleukin-24