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.