Interleukin-17 stimulates chemokine (interleukin-8 and monocyte chemoattractant protein-1) secretion in human pancreatic periacinar myofibroblasts.

摘要

BACKGROUND: Interleukin (IL)-17 is a newly identified T-cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of CD4+ T-cell-derived cytokines on chemokine secretion in human pancreatic periacinar myofibroblasts. METHODS: The secretion of IL-8 and monocyte chemoattractant protein (MCP)-1 was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analyzed by Northern blot and a binding assay using 125I-labeled IL-17. The activation of nuclear factor-kappaB (NF-kappaB) was assessed by an electrophoretic gel mobility shift assay (EMSA). RESULTS: IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h. and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL-8 secretion and additively enhanced MCP-1 secretion. IFN-gamma induced a weak increase in IL-17R mRNA abundance, but incubation with IFN-gamma for 24 h had no effects on 125I-labeled IL-17-binding, indicating that the co-stimulatory effects of IL-17 and IFN-gamma were not regulated by the modulation of IL-17R expression. Furthermore, IL-17 induced a rapid increase in NF-kappaB DNA-binding activity, and the combination of IL-17 and IFN-gamma further enhanced NF-kappaB DNA-binding activity. CONCLUSIONS: In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion in human pancreatic periacinar myofibroblasts. The combination of IL-17 with IFN-gamma further enhances chemokine secretion. These findings indicate a linkage between T-cell-mediated immunity and inflammatory responses in the pancreas.