IL-13 promotes the proliferation of rat pancreatic stellate cells through the suppression of NF-{kappa}B/TGF-{beta}{sub 1} pathway

Journal Article · Fri Feb 26 00:00:00 EST 2010 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2010.01.078· OSTI ID:22202390

Shinozaki, Satoshi ^[1]; Mashima, Hirosato ^[2]; Ohnishi, Hirohide ^[2]; Sugano, Kentaro ^[1]

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1. Division of Gastroenterology, Department of Medicine, Jichi Medical University, Tochigi 329-0498 (Japan)
2. Department of Gastroenterology, Akita University Graduate School of Medicine, Akita 010-8543 (Japan)

In chronic pancreatitis, pancreatic stellate cells (PSCs) play a central role in tissue fibrogenesis. Transforming growth factor {beta}{sub 1} (TGF-{beta}{sub 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}{sub 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}{sub 1}. IL-13 enhanced Stat6 phosphorylation in PSCs but Stat6 was not involved in the suppression of TGF-{beta}{sub 1}. IL-13 inhibited the transcriptional activity of NF-{kappa}B, and the expression of mutant I-{kappa}B reproduced the suppression of autocrine TGF-{beta}{sub 1} and promoted PSCs proliferation. Taken together, we demonstrated that IL-13 promotes PSCs proliferation through the suppression of the transcriptional activity of NF-{kappa}B, resulting in the decrease of autocrine TGF-{beta}{sub 1}. This finding provides an unequivocal evidence of IL-13 participation in pancreatic fibrosis, illustrating a new strategy for chronic pancreatitis.

• OSTI ID: 22202390
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 393, Issue 1; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACTIN
ANIMAL TISSUES
DIGESTIVE SYSTEM DISEASES
ENZYME IMMUNOASSAY
FIBROSIS
IMMUNOGLOBULINS
INFLAMMATION
LIVER
LYMPHOKINES
MUSCLES
MUTANTS
PANCREAS
PEROXIDASES
PHOSPHORYLATION
RATS
TRANSCRIPTION
TRANSDUCERS