IL-13 promotes the proliferation of rat pancreatic stellate cells through the suppression of NF-kappaB/TGF-beta1 pathway.

Authors: Shinozaki, S  Mashima, H  Ohnishi, H  Sugano, K 
Citation: Shinozaki S, etal., Biochem Biophys Res Commun. 2010 Feb 26;393(1):61-5. Epub 2010 Jan 25.
Pubmed: (View Article at PubMed) PMID:20100461
DOI: Full-text: DOI:10.1016/j.bbrc.2010.01.078

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.

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CRRD Object Information
CRRD ID: 4145466
Created: 2010-11-04
Species: All species
Last Modified: 2010-11-04
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.