Fibroblast growth factor-2 stimulates interleukin-6 secretion in human pancreatic periacinar myofibroblasts

Akira Andoh, Shigeki Bamba, Sanae Fujino, Osamu Inatomi, Zhuobin Zhang, Shokei Kim, Atsushi Takayanagi, Nobuyoshi Shimizu, Yoshihide Fujiyama

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Objectives: Fibroblast growth factor-2 (FGF-2) plays an important role in the pathophysiology of acute and chronic pancreatitis. In the present study, to evaluate the proinflammatory nature of FGF-2, we investigated the effects of FGF-2 on IL-6 secretion in human pancreatic periacinar myofibroblasts. Methods: IL-6 supernatant levels were determined by enzyme-linked immunosorbent assays (ELISA). IL-6 mRNA expression were determined by Northern blots and quantitative PCRs. Activated protein (AP)-1 DNA-binding activities were evaluated by electrophoretic gel mobility shift assays (EMSA). Results: FGF-2 induced IL-6 release in a dose- and time-dependent manner. FGF-2 activity for IL-6 induction was the same as that of IL-17. The combination of FGF-2 and IL-17 exerted additive effects at mRNA and protein levels. FGF-2 induced AP-1 DNA-binding activity, but blockage of AP-1 signaling by adenovirus-mediated transfer of a dominant negative c-Jun gene did not affect FGF-2-induced IL-6 mRNA expression. FGF-2 rapidly induced activation of ERK1/2 and p38 MAP kinases, and specific inhibitors for these enzymes significantly reduced FGF-2-induced IL-6 release. Conclusion: In the pancreas, FGF-2 may not only play a role as a growth factor in tissue injury repair processes but also as an inducer of acute-phase response via stimulation of IL-6 release.

Original languageEnglish
Pages (from-to)278-283
Number of pages6
JournalPancreas
Volume29
Issue number4
DOIs
Publication statusPublished - 2004 Nov

Keywords

  • Activated protein 1
  • Inflammation
  • Mitogen-activated protein kinase
  • Nuclear factor κB

ASJC Scopus subject areas

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

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