IL-13 promotes the proliferation of rat pancreatic stellate cells through the suppression of NF-kappaB/TGF-beta1 pathway.
In chronic pancreatitis, pancreatic stellate cells (PSCs) play a central role in tissue fibrogenesis. Transforming growth factor beta(1) (TGF-beta(1)) and the Th2 lymphokines such as interleukin (IL)-13 are major profibrogenic cytokines in many organs. Activated PSCs produce various inflammatory cytokines including TGF-beta(1). In this study, we investigated whether IL-13 affects pancreatic fibrogenesis by modulating the functions of PSCs. IL-13 promoted PSCs proliferation without activation through the suppression of autocrine TGF-beta(1). IL-13 enhanced Stat6 phosphorylation in PSCs but Stat6 was not involved in the suppression of TGF-beta(1). IL-13 inhibited the transcriptional activity of NF-kappaB, and the expression of mutant I-kappaB reproduced the suppression of autocrine TGF-beta(1) and promoted PSCs proliferation. Taken together, we demonstrated that IL-13 promotes PSCs proliferation through the suppression of the transcriptional activity of NF-kappaB, resulting in the decrease of autocrine TGF-beta(1). This finding provides an unequivocal evidence of IL-13 participation in pancreatic fibrosis, illustrating a new strategy for chronic pancreatitis.
Shinozaki
Satoshi
S
Division of Gastroenterology, Department of Medicine, Jichi Medical University, Tochigi 329-0498, Japan.
Mashima
Hirosato
H
Ohnishi
Hirohide
H
Sugano
Kentaro
K
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005355:Fibrosis; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology*; D050500:Pancreatitis, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000235:genetics
D018793:Interleukin-13; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D053773:Transforming Growth Factor beta1