Association between chronic liver and colon inflammation during the development of murine syngeneic graft-versus-host disease.
Association between chronic liver and colon inflammation during the development of murine syngeneic graft-versus-host disease.
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DOI：
10.1152/ajpgi.00511.2009
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发表时间：
2010-07
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影响因子：
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通讯作者：
J. Brandon;Jacqueline Perez;C. D. Jennings;D. Cohen;Vishal J. Sindhava;S. Bondada;Alan M. Kaplan;Alan M. Kaplan;J. Bryson
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文献类型：
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作者：
J. Brandon;Jacqueline Perez;C. D. Jennings;D. Cohen;Vishal J. Sindhava;S. Bondada;Alan M. Kaplan;Alan M. Kaplan;J. Bryson
环孢素A （CsA）诱导的同源移植物抗宿主病（SGVHD）小鼠模型是一种骨髓（BM）移植模型，其发展为慢性结肠炎症，与其他小鼠CD4(+) T细胞介导的结肠炎模型相同。有趣的是，SGVHD动物出现的慢性肝脏病变与临床慢性肝病的早期胆道周围炎症阶段相似，后者通常与炎症性肠病（IBD）相关。因此，研究人员开始研究在SGVHD模型中发生的慢性肝脏炎症。为了诱导SGVHD，小鼠采用致死性照射、同源骨髓重组和CsA处理。所有发生结肠炎的SGVHD动物也会发生慢性肝脏炎症。对对照组和SGVHD动物的肝脏样本进行组织病理学监测，检测炎症介质的RNA，以及炎症浸润的表型分析和体外反应性。患病动物出现肝内和肝外胆管病变。慢性肝脏炎症相关分子mRNA水平升高，包括粘膜细胞粘附分子-1、趋化因子CCL25、CCL28、CCR9和T(H)1-和T(H)17相关细胞因子。CD4(+) T细胞定位于患病动物肝脏的胆道周围区域，观察到肝脏相关单核细胞对结肠细菌抗原的增殖反应增强。小鼠SGVHD结肠炎模型可能是研究慢性结肠炎症与炎症性肝病之间肠-肝联系的有价值的工具。
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(H)1- and T(H)17-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.