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

Osamu Inatomi, Akira Andoh, Yuhki Yagi, Atsuhiro Ogawa, Kazunori Hata, Hisanori Shiomi, Tohru Tani, Atsushi Takayanagi, Nobuyoshi Shimizu, Yoshihide Fujiyama

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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-1β, and tumor necrosis factor (TNF) -α, respectively. The effects of IL-17 were detected as similar in extent to those induced by IL-1β or TNF-α. Costimulation by IL-17 plus IL-1β and/or IL-17 plus TNF-α 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 IκBα markedly inhibited the effects of IL-17, IL-1β, and TNF-α. Mitogen-activated protein kinase inhibitors (U0126, PD098059, and SB203580) also blocked MMP-3 secretion. These findings indicate a role for nuclear factor-κB 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-1β, and TNF-α. Pancreatic myofibroblasts may play an important role in extracellular matrix turnover via MMP-3 secretion in the pancreas.

Original languageEnglish
Pages (from-to)126-132
Number of pages7
JournalPancreas
Volume34
Issue number1
DOIs
Publication statusPublished - 2007 Jan 1

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Keywords

  • Chronic pancreatitis
  • Extracellular matrix
  • Fibrosis
  • NF-κB

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

Inatomi, O., Andoh, A., Yagi, Y., Ogawa, A., Hata, K., Shiomi, H., Tani, T., Takayanagi, A., Shimizu, N., & Fujiyama, Y. (2007). Matrix metalloproteinase-3 secretion from human pancreatic periacinar myofibroblasts in response to inflammatory mediators. Pancreas, 34(1), 126-132. https://doi.org/10.1097/01.mpa.0000246662.23128.57