ePrints

Endogenous interleukin-10 modulates fibrosis and regeneration in experimental chronic pancreatitis

Lookup NU author(s): Professor Albert Geerts

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

Interleukin (IL)-10, a potent anti-inflammatory cytokine, limits the severity of acute pancreatitis and downregulates transforming growth factor (TGF)-beta release by inflammatory cells on stimulation. Proinflammatory mediators, reactive oxygen species, and TGF-beta can activate pancreatic stellate cells and their synthesis of collagen I and III. This study evaluates the role of endogenous IL-10 in the modulation of the regeneration phase following acute pancreatitis and in the development of pancreatic fibrosis. IL-10 knockout (KO) mice and their C57BL/6 controls were submitted to repeated courses (3/wk, during 6 wk, followed by 1 wk of recovery) of cerulein-induced acute pancreatitis. TGF-beta(1) release was measured on plasma, and its pancreatic expression was assessed by quantitative RT-PCR and immunohistochemistry. Intrapancreatic IL-10 gene expression was assessed by semiquantitative RT-PCR, and intrapancreatic collagen content was assessed by picrosirius staining. Activated stellate cells were detected by immunohistochemistry. S phase intrapancreatic cells were marked using tritiated thymidine labeling. After repeated acute pancreatitis, IL-10 KO mice had more severe histological lesions and fibrosis (intrapancreatic collagen content) than controls. TGF-beta(1) plasma levels, intrapancreatic transcription, and expression by ductal and interstitial cells, as well as the number of activated stellate cells, were significantly higher. IL-10 KO mice disclosed significantly fewer acinar cells in S phase, whereas the opposite was observed for pseudotubular cells. Endogenous IL-10 controls the regeneration phase and limits the severity of fibrosis and glandular atrophy induced by repeated episodes of acute pancreatitis in mice.

Publication metadata

Author(s): Demols A, Van Laethem JL, Quertinmont E, Degraef C, Delhaye M, Geerts A, Deviere J

Publication type: Article

Publication status: Published

Journal: American Journal of Physiology: Gastrointestinal and Liver Physiology

Year: 2002

Volume: 282

Issue: 6

Pages: G1105-G1112

ISSN (print): 0193-1857

ISSN (electronic): 1522-1547

Publisher: American Physiological Society

URL: http://dx.doi.org/10.1152/ajpgi.00431.2001

DOI: 10.1152/ajpgi.00431.2001

Altmetrics

Share