Proinflammatory cytokines regulate LOX-1 expression in vascular smooth muscle cells

被引:86
作者
Hofnagel, O
Luechtenborg, B
Stolle, K
Lorkowski, S
Eschert, H
Plenz, G
Robenek, H
机构
[1] Univ Munster, Inst Arteriosclerosis Res, D-48149 Munster, Germany
[2] Hosp Univ Muenster, Dept Cardiol & Angiol, Munster, Germany
[3] Hosp Univ Muenster, Dept Thorac & Cardiovasc Surg, Munster, Germany
关键词
atherosclerosis; LOX-1; scavenger receptor; smooth muscle cell; interleukin;
D O I
10.1161/01.ATV.0000140061.89096.2b
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective - Atherogenesis represents a type of chronic inflammation and involves elements of the immune response, eg, the expression of proinflammatory cytokines. In advanced atherosclerotic lesions, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is expressed in endothelial cells, macrophages, and smooth muscle cells (SMCs). In vitro, the expression of LOX-1 is induced by inflammatory cytokines like TNF-alpha and transforming growth factor (TGF)-beta. Therefore, LOX-1 is thought to be upregulated locally in response to cytokines in vivo. Methods and Results - We determined by reverse-transcription polymerase chain reaction (PCR) and Western blot analysis whether the mediators of the acute phase response in inflammation, IL-1alpha, IL-1beta, and TNF-alpha, regulate LOX-1 expression in cultured SMC, and whether this regulation is influenced by peroxisome proliferator-activated receptor gamma (PPARgamma). We studied by immunohistochemistry whether these cytokines are spatially correlated with LOX-1 expression in advanced atherosclerotic lesions. We found upregulation of LOX-1 expression in SMC in a dose- and time-dependent manner after incubation with IL-1alpha, IL-1beta, and TNF-alpha. Simultaneous incubation with these cytokines at saturated concentrations had an additive effect on LOX-1 expression. The PPARgamma activator, 15d-PGJ(2), however, inhibited IL-1beta-induced upregulation of LOX-1. In the intima of atherosclerotic lesions regions of IL-1alpha, IL- 1beta, and TNF-alpha expression corresponded to regions of LOX-1 expression. Conclusion - We suppose that upregulated LOX-1 expression in SMC of advanced atherosclerotic lesions is a response to these proinflammatory cytokines. Moreover, the proinflammatory effects of these cytokines can be decreased by the antiinflammatory effect of PPARgamma.
引用
收藏
页码:1789 / 1795
页数:7
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