Abstract
A variety of hepatobiliary abnormalities have been described in patients with chronic inflammatory bowel diseases (IBDs). The purpose of this study was to investigate the role of endogenous IL-10 in alteration of hepatocyte TJ paracellular barrier and in the rapid transcytotic vesicular pathway modification associated with intestinal inflammation. To address this question, we used an experimental model of colitis, induced by dinitrobenzene sulfonic acid (DNBS). When compared to DNBS-treated IL-10 wild-type (IL-10WT) mice, DNBS-treated IL-10 knock-out mice (IL-10KO) mice experienced a higher rate of the extent and severity of the histological signs of colon injury. Colon and liver levels of the pro-inflammatory cytokines tumour necrosis factor, interleukin-1 beta and interleukin-6 were also greatly enhanced in IL-10KO mice in comparison to wild-type mice. Liver histology from IL-10KO and IL-10WT did not show any parenchymal and portal tract inflammation at 4 days after DNBS administration. Serum total bilirubin and Alanine aminotransferase, were significantly increased in DNBS-IL-10KO mice vs. DNBS-IL-10KO mice. Therefore, we found an increase of tight junctional permeability to lanthanum nitrate (molecular weight, 433) in the livers from DNBS-treated IL-10WT mice; lanthanum accumulated throughout the junctional area up to the most apical region bordering the lumen. Absence of a functional IL-10 gene in IL-10KO mice resulted in a significant augmentation of apical diffusion of lanthanum after DNBS-induced colitis. Immunofluorescent labelling of frozen liver sections from DNBS-IL10KO mice, immunolocalization for and claudin-1 and ZO-1 resulted in a significant alteration in the localization of the immunosignals for claudin-1 and ZO-1 after DNBS administration in comparison with DNBS-IL10WT. In conclusion, we suggest that the absence of IL-10 may represent an important pathophysiological mechanism of hepatobiliary injuries and cholestasis observed in patients with IBD.
Highlights
A variety of hepatobiliary abnormalities have been described in patients with chronic inflammatory bowel diseases (IBDs)
In conclusion, we suggest that the absence of IL-10 may represent an important pathophysiological mechanism of hepatobiliary injuries and cholestasis observed in patients with IBD
The objective of the present study was to investigate the role of IL-10 on the hepatic TJ permeability alteration during dinitrobenzene sulfonic acid (DNBS)-induced experimental colitis
Summary
A variety of hepatobiliary abnormalities have been described in patients with chronic inflammatory bowel diseases (IBDs). The prevalence of abnormal liver function tests in patients with ulcerative colitis and Crohn’s disease may be as high as 17% [1]. It has long been known that serum total bilirubin and aminotransferase and alkaline phosphatase activities can be increased in patients with ulcerative colitis. Analysis of liver biopsy specimens from patients with IBD can show inflammation of portal areas, cholangitis, and primary sclerosing colangitis. Results: Colon and liver levels of the pro-inflammatory cytokines tumour necrosis factor, interleukin-1 and interleukin-6 were greatly enhanced in IL-10KO mice in comparison to wild-type mice. Serum total bilirubin and Alanine aminotransferase, were significantly increased in DNBS-IL10KO mice vs. DNBS-IL-10KO mice
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