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Am J Physiol Gastrointest Liver Physiol 282: G1105-G1112, 2002; doi:10.1152/ajpgi.00431.2001
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Vol. 282, Issue 6, G1105-G1112, June 2002

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

Anne Demols1,2, Jean-Luc Van Laethem1,2, Eric Quertinmont2, Chantal Degraef3, Myriam Delhaye1,2, Albert Geerts4, and Jacques Deviere1,2

1 Department of Gastroenterology, 2 Hôpital Erasme and Laboratory of Experimental Gastroenterology, and 3 Laboratory of Experimental Cytology and Cancerology, Université Libre de Bruxelles, B 1070 Brussels, Belgium; and 4 Department of Medical Cell Biology, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne NE2 4HH, United Kingdom

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.

experimental chronic pancreatitis; pancreatic fibrosis; transforming growth factor-beta ; pancreatic stellate cells


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