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


CONCLUSIONS
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.
Andoh
Akira
A
Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan. andoh@belle.shiga-med.ac.jp
Bamba
Shigeki
S
Fujino
Sanae
S
Inatomi
Osamu
O
Zhang
Zhuobin
Z
Kim
Shokei
S
Takayanagi
Atsushi
A
Shimizu
Nobuyoshi
N
Fujiyama
Yoshihide
Y
D000256:Adenoviridae; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D018014:Gene Transfer Techniques; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009154:Mutation / Q000235:genetics / Q000502:physiology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D020381:Interleukin-17; D015850:Interleukin-6; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D016222:Fibroblast Growth Factor 2; D020928:Mitogen-Activated Protein Kinases