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

• DOI: 10.1152/ajpgi.00431.2001
• Publication Date: 2015-03-03T14:55:16Z
• Authors: Anne Demols; Jean-Luc Van Laethem; Eric Quertinmont; Chantal Degraef; Myriam Delhaye; Albert Geerts; Jacques Deviere
• Keywords: Gene Expression -- immunology; 0301 basic medicine; Transcription, Genetic; Collagen -- metabolism; Knockout; Down-Regulation -- immunology; Down-Regulation; Gene Expression; Pancreatitis -- immunology; Pancreatitis -- metabolism; Inbred C57BL; Transforming Growth Factor beta1; Mice; 03 medical and health sciences; Recurrence; Transforming Growth Factor beta; Interleukin-10 -- metabolism; Regeneration -- immunology; Animals; Regeneration; Pancreas; Cell Division -- immunology; Mice, Knockout; Pancreatitis -- pathology; Pancreas -- physiology; Sciences bio-médicales et agricoles; Fibrosis; Interleukin-10; 3. Good health; Mice, Inbred C57BL; Pancreatitis; Acute Disease; Chronic Disease; Genetic -- immunology; Collagen; Atrophy; Transcription; Interleukin-10 -- genetics; Cell Division; Pancreas -- pathology; Transforming Growth Factor beta -- genetics

Interleukin (IL)-10, a potent anti-inflammatory cytokine, limits the severity of acute pancreatitis and downregulates transforming growth factor (TGF)-β release by inflammatory cells on stimulation. Proinflammatory mediators, reactive oxygen species, and TGF-β 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-β1 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-β1 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.