Association Between Chronic Liver and Colon Inflammation During the Development of Murine Syngeneic Graft-Versus-Host Disease

Authors

Jason Anthony Brandon, University of KentuckyFollow
Jacqueline Perez-Rodriguez, University of KentuckyFollow
C. Darrell Jennings, University of KentuckyFollow
Donald A. Cohen, University of KentuckyFollow
Vishal J. Sindhava, University of KentuckyFollow
Subbarao Bondada, University of KentuckyFollow
Alan M. Kaplan, University of KentuckyFollow
J. Scott Bryson, University of KentuckyFollow

Abstract

The murine model of cyclosporine A (CsA)-induced syngeneic graft-versus-host disease (SGVHD) is a bone marrow (BM) transplantation model that develops chronic colon inflammation identical to other murine models of CD4⁺ T cell-mediated colitis. Interestingly, SGVHD animals develop chronic liver lesions that are similar to the early peribiliary inflammatory stages of clinical chronic liver disease, which is frequently associated with inflammatory bowel disease (IBD). Therefore, studies were initiated to investigate the chronic liver inflammation that develops in the SGVHD model. To induce SGVHD, mice were lethally irradiated, reconstituted with syngeneic BM, and treated with CsA. All of the SGVHD animals that developed colitis also develop chronic liver inflammation. Liver samples from control and SGVHD animals were monitored for tissue pathology, RNA for inflammatory mediators, and phenotypic analysis and in vitro reactivity of the inflammatory infiltrate. Diseased animals developed lesions of intrahepatic and extrahepatic bile ducts. Elevated levels of mRNA for molecules associated with chronic liver inflammation, including mucosal cellular adhesion molecule −1, the chemokines CCL25, CCL28, CCR9, and T_H1- and T_H17-associated cytokines were observed in livers of SGVHD mice. CD4⁺ T cells were localized to the peribiliary region of the livers of diseased animals, and an enhanced proliferative response of liver-associated mononuclear cells against colonic bacterial antigens was observed. The murine model of SGVHD colitis may be a valuable tool to study the entero-hepatic linkage between chronic colon inflammation and inflammatory liver disease.

Document Type

Article

Publication Date

9-1-2010

Notes/Citation Information

Published in American Journal of Physiology: Gastrointestinal and Liver Physiology, v. 299, issue 3, p. G602-G613.

Copyright © 2010 by the American Physiological Society

The copyright holder has granted the permission for posting the article here.

The document available for download is the authors' post-peer-review final draft of the article.

Digital Object Identifier (DOI)

https://doi.org/10.1152/ajpgi.00511.2009

Funding Information

This work was supported by National Institutes of Health Grant PO1 CA092372 (J. S. Bryson).

Related Content

Supplemental information for this article can be found at: https://www.physiology.org/doi/suppl/10.1152/ajpgi.00511.2009

Repository Citation

Brandon, Jason Anthony; Perez-Rodriguez, Jacqueline; Jennings, C. Darrell; Cohen, Donald A.; Sindhava, Vishal J.; Bondada, Subbarao; Kaplan, Alan M.; and Bryson, J. Scott, "Association Between Chronic Liver and Colon Inflammation During the Development of Murine Syngeneic Graft-Versus-Host Disease" (2010). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 125.
https://uknowledge.uky.edu/microbio_facpub/125