Matrix metalloproteinase-3 secretion from human pancreatic periacinar myofibroblasts in response to inflammatory mediators - PubMed (original) (raw)

Matrix metalloproteinase-3 secretion from human pancreatic periacinar myofibroblasts in response to inflammatory mediators

Osamu Inatomi et al. Pancreas. 2007 Jan.

Abstract

Objectives: Matrix metalloproteinases (MMPs) play roles in the pathophysiology of pancreatic disorders. However, the regulation of MMP-3 secretion in the pancreas remains unclear. In this study, we assessed the expression of MMP-3 in human pancreatic periacinar myofibroblasts.

Methods: MMP-3 secretion and MMP-3 mRNA expression were determined by enzyme-linked immunosorbent assay and real-time polymerase chain reaction, respectively.

Results: In human pancreatic myofibroblasts, MMP-3 secretion and mRNA expression were induced by interleukin (IL)-17, IL-1beta, and tumor necrosis factor (TNF) -alpha, respectively. The effects of IL-17 were detected as similar in extent to those induced by IL-1beta or TNF-alpha. Costimulation by IL-17 plus IL-1beta and/or IL-17 plus TNF-alpha induced a synergistic increase in MMP-3 secretion, although the costimulatory effects of these combinations were not detected in tissue inhibitor of matrix metalloproteinase-1 secretion. Adenovirus-mediated transfer of a stable form of IkappaBalpha markedly inhibited the effects of IL-17, IL-1beta, and TNF-alpha. Mitogen-activated protein kinase inhibitors (U0126, PD098059, and SB203580) also blocked MMP-3 secretion. These findings indicate a role for nuclear factor-kappaB and mitogen-activated protein kinases in cytokine-induced MMP-3 secretion.

Conclusions: Pancreatic periacinar myofibroblasts actively secrete MMP-3 in response to IL-17, IL-1beta, and TNF-alpha. Pancreatic myofibroblasts may play an important role in extracellular matrix turnover via MMP-3 secretion in the pancreas.

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