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.
MeSH terms
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Enzyme-Linked Immunosorbent Assay
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Gene Expression / drug effects
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Humans
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Interleukin-1beta / pharmacology*
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Interleukins / genetics
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Interleukins / metabolism*
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / metabolism
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Myofibroblasts / cytology
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Myofibroblasts / metabolism*
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Pancreatitis, Chronic / genetics
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Pancreatitis, Chronic / metabolism*
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Pancreatitis, Chronic / pathology
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Pancreatitis, Chronic / physiopathology*
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation / drug effects
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Primary Cell Culture
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Protein Kinase Inhibitors / pharmacology*
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RNA, Messenger / biosynthesis
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Real-Time Polymerase Chain Reaction
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Receptors, Interleukin / genetics
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Receptors, Interleukin / metabolism*
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Signal Transduction / drug effects
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / genetics
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Interleukin-1beta
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Interleukins
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors
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RNA, Messenger
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Receptors, Interleukin
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Transcription Factor AP-1
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interleukin-24
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases