Cholangiocyte secretion of chemokines in experimental biliary atresia.

Cholangiocyte secretion of chemokines in experimental biliary atresia.
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DOI:
10.1016/j.jpedsurg.2008.07.007
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发表时间:
2009-03
影响因子:
2.4
通讯作者:
Tiao, Greg
Tiao, Greg
中科院分区:
医学3区
文献类型:
--
作者:
Jafri, Mubeen;Donnelly, Bryan;Bondoc, Alex;Allen, Steven;Tiao, Greg

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胆道闭锁(BA)是一种新生儿疾病,其导致胆道系统阻塞。BA的病因尚不清楚;然而,最近使用胆道闭锁小鼠模型的研究发现,轮状病毒感染胆道上皮细胞(胆管细胞)引发炎症反应。我们假设轮状病毒感染胆管细胞导致宿主免疫反应的重要介质--趋化因子的释放。在体实验中,Balb/c幼鼠分别注射恒河猴轮状病毒(RRV)或生理盐水,于注射后2、5、7和14 d显微解剖肝外胆管。接下来,将永生化胆管细胞系(mCl)与RRV或无血清培养基一起孵育。采用ELISA、PCR和免疫组化法进行定性和定量趋化因子测定。在体内,增加的水平的趋化因子MIP-2,MCP-1,KC和RANTES被发现在RRV感染的小鼠胆管。在体外,受感染的mCl细胞产生的这些相同的趋化因子的剂量和时间的关系。这些新的结果表明,RRV感染的胆管细胞表达趋化因子可能引发宿主炎症过程,导致胆管梗阻。了解病毒感染如何启动这种反应可能有助于阐明胆道闭锁的发病机制。
Biliary atresia (BA) is a disease of the newborn which results in obstruction of the biliary tree. The cause of BA remains unknown; however, recent studies using the murine model of biliary atresia have found that rotavirus infection of the biliary epithelial cell (cholangiocyte) triggers an inflammatory response. We hypothesized that rotavirus infection of cholangiocytes results in the release of chemokines, important mediators of the host immune response. In vivo, Balb/c pups were injected with rhesus rotavirus (RRV) or saline, and, their extrahepatic bile ducts were microdissected 2,5, 7, and 14 days after injection. Next, an immortalized cholangiocyte cell line (mCl) was incubated with RRV or serum free media. Qualitative and quantitative chemokine assement was performed using ELISA, PCR, and immunohistchemistry. In vivo, increased levels of the chemokines MIP-2, MCP-1, KC and RANTES were found in RRV-infected murine bile ducts. In vitro, infected mCl cells produced increasing amounts of these same chemokines in relation to dose and time. These novel results suggest that chemokine expression by RRV-infected cholangiocytes may trigger a host inflammatory process that causes bile duct obstruction. Understanding how viral infection initiates this response may shed light on the pathogenesis of biliary atresia.
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发表时间: 2007-08-01
期刊: SURGERY
影响因子: 3.8
作者:
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