Decreased intercellular communication and connexin expression in mouse aortic endothelium during lipopolysaccharide-induced inflammation
Decreased intercellular communication and connexin expression in mouse aortic endothelium during lipopolysaccharide-induced inflammation
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DOI：
10.1159/000079614
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发表时间：
2004-01-01
影响因子：
1.7
通讯作者：
Ouellette, Y
中科院分区：
文献类型：
--
作者：
Simon, AM;McWhorter, AR;Ouellette, Y
间隙连接细胞间通讯在炎症过程中的作用还不清楚。特别是，血管内皮连接蛋白（间隙连接蛋白）的表达和功能的变化，在炎症介质的反应还没有得到充分的研究。在这项研究中，我们使用细胞间染料转移的方法来评估内皮细胞间的通信在主动脉段分离的小鼠腹腔内脂多糖（LPS），一种有效的炎症介质处理或不处理。LPS处理导致注射后18小时内皮染料偶联减少49%。Western印迹表明，LPS治疗也导致内皮连接蛋白40（Cx40）水平降低至对照水平的33%。连接蛋白37（Cx 37）水平在LPS处理后仅略微下降至对照水平的79%。我们还检查了Cx 37（-/-）和Cx40（-/-）小鼠主动脉段的内皮通讯。与来自Cx40（-/-）动物的内皮相比，LPS处理导致从Cx 37（-/-）动物分离的内皮中的染料转移显著更大的降低（71%对26%降低）。LPS注射引起Cx 37（-/-）内皮细胞中Cx40水平降低，而LPS实际上增加Cx40（-/-）内皮细胞中Cx 37水平。这些结果表明，LPS至少部分通过调节Cx40和Cx 37水平来介导内皮缝隙连接介导的通讯的变化。版权所有（C）2004 S. Karger AG，巴塞尔。
The role of gap junctional intercellular communication during inflammatory processes is not well understood. In particular, changes in the expression and function of vascular endothelial connexins ( gap junction proteins) in response to inflammatory agents has not been fully investigated. In this study, we used intercellular dye transfer methods to assess interendothelial communication in aortic segments isolated from mice treated with or without intraperitoneal lipopolysaccharide (LPS), a potent inflammatory mediator. LPS treatment resulted in a 49% decrease in endothelial dye coupling 18 h after injection. Western blots indicated that LPS treatment also caused a reduction in endothelial connexin40 (Cx40) levels to 33% of control levels. Connexin37 (Cx37) levels decreased only slightly after LPS treatment to 79% of control levels. We also examined endothelial communication in aortic segments isolated from Cx37(-/-) and Cx40(-/-) mice. LPS treatment caused a significantly greater decrease in dye transfer in endothelium isolated from Cx37(-/-) animals compared with endothelium from Cx40(-/-) animals (71 vs. 26% decrease). LPS injection caused a reduction in Cx40 levels in Cx37(-/-) endothelium, whereas LPS actually increased Cx37 levels in Cx40(-/-) endothelium. These results suggest that LPS mediates changes in endothelial gap junction-mediated communication, at least in part, through modulation of Cx40 and Cx37 levels. Copyright (C) 2004 S. Karger AG, Basel.