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

研究成果: Article査読

14 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)126-132
ページ数7
ジャーナルPancreas
34
1
DOI
出版ステータスPublished - 2007 1月
外部発表はい

ASJC Scopus subject areas

  • 内科学
  • 内分泌学、糖尿病および代謝内科学
  • 肝臓学
  • 内分泌学

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