首页> 外文期刊>American Journal of Physiology >Regulation of hepatic connexins in cholestasis: possible involvement of Kupffer cells and inflammatory mediators.
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Regulation of hepatic connexins in cholestasis: possible involvement of Kupffer cells and inflammatory mediators.

机译:胆汁淤积中肝连接蛋白的调节:库普弗细胞和炎性介质的可能参与。

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摘要

Hepatocyte gap junction proteins, connexins (Cxs) 26 and 32, are downregulated during obstructive cholestasis (OC) and lipopolysaccharide hepatocellular cholestasis (LPS-HC). We investigated rat hepatic Cxs during ethynylestradiol hepatocellular cholestasis (EE-HC) and choledochocaval fistula (CCF) and compared them with OC and LPS-HC. Levels (immunoblotting) and cellular distribution (immunofluorescence) of Cx26, -32, and -43, as well as macrophage infiltration, were studied in livers of rats under each condition. Cx26 and -32 were reduced in LPS-HC, OC, and CCF. However, in EE-HC, Cx26 did not change and Cx32 was increased. Prominent inflammation occurred in LPS-HC, OC, and CCF, which was associated with increased levels of Cx43 in LPS-HC and OC but not CCF. No inflammation nor changes in Cx43 levels occurred during EE-HC. In cultured hepatocytes, dye coupling was reduced by tumor necrosis factor-alpha and interleukins-1beta and -6, whereas reduction induced by LPS required coculture with Kupffer cells. Thus hepatocyte gap junctions are downregulated in forms of cholestasis associated with inflammation, and reduced intercellular communication might be induced in part by proinflammatory mediators.
机译:在阻塞性胆汁淤积(OC)和脂多糖肝细胞胆汁淤积(LPS-HC)期间,肝细胞间隙连接蛋白,连接蛋白(Cxs)26和32被下调。我们调查了在乙炔雌二醇肝细胞胆汁淤积(EE-HC)和胆总管瘘(CCF)期间的大鼠肝Cxs,并将它们与OC和LPS-HC进行了比较。研究了每种条件下大鼠肝脏中Cx26,-32和-43的水平(免疫印迹)和细胞分布(免疫荧光),以及巨噬细胞浸润。 Cx26和-32在LPS-HC,OC和CCF中降低。但是,在EE-HC中,Cx26不变,而Cx32增加。 LPS-HC,OC和CCF中发生明显的炎症,这与LPS-HC和OC中Cx43的水平升高有关,但与CCF无关。在EE-HC期间没有发炎或Cx43水平没有变化。在培养的肝细胞中,肿瘤坏死因子-α和白介素-1β和-6减少了染料偶联,而LPS诱导的减少需要与库普弗细胞共培养。因此,肝细胞间隙连接以与炎症相关的胆汁淤积的形式被下调,并且促炎性介质可能部分地引起细胞间通讯的减少。

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