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.