کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2795618 | 1155336 | 2007 | 6 صفحه PDF | دانلود رایگان |
Multiple pro-inflammatory mediators contribute to cardiac dysfunction caused by bacterial lipopolysaccharide (LPS). The rapid TNF-α response is likely involved in the induction of down-stream myocardial depressant factors. Studies by our laboratory and others indicate an important role for ICAM-1 in endotoxemic cardiac dysfunction through leukocyte-independent mechanisms. The purpose of this study was to determine: whether ICAM-1 knockout improves cardiac function during endotoxemia and whether TLR4 and TNF-α regulate LPS-induced myocardial ICAM-1 expression. Methods and results. Mice were treated with Escherichia coli LPS (0.5 mg/kg iv). Myocardial ICAM-1 levels were analyzed by immunoblotting and left ventricular developed pressure (LVDP) was assessed by the Langendorff technique. In wild-type mice, peak ICAM-1 levels were observed at 4 h when myocardial contractility was depressed. Myocardial contractility was improved following LPS in mice lacking functional TLR4, TNF-α or ICAM-1. TLR4 mutation abolished ICAM-1 expression with abrogation of precedent TNF-α response. Similarly, TNF-α knockout reduced myocardial ICAM-1 level following LPS treatment. Conclusions. ICAM-1 contributes to the mechanism of endotoxemic cardiac dysfunction. TNF-α is involved in the regulation of myocardial ICAM-1 expression by TLR4.
Journal: Cytokine - Volume 38, Issue 3, June 2007, Pages 124–129