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Cardiovascular Research 2002 53(2):524-532; doi:10.1016/S0008-6363(01)00491-6
© 2002 by European Society of Cardiology
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Copyright © 2001, European Society of Cardiology

OxLDL upregulates CXCR2 expression in monocytes via scavenger receptors and activation of p38 mitogen-activated protein kinase

Zhu-Bin Leia,*, Zhe Zhangb, Qing Jingc, Yong-Wen Qinc, Gang Peib, Beng-Zhen Caoa and Xiao-Yan Lia

aDepartment of Cardiology, General Hospital of Jinan Military Area, Jinan 250031, China
bShanghai Institute of Cell Biology and Shanghai Research Center of Life Sciences, Chinese Academy of Sciences, Shanghai, China
cChanghai Hospital, Second Military Medical University, Shanghai, China

* Corresponding author. Tel.: +86-531-798-6563 leizhubin88{at}email.com.cn

Objective: Chemokine receptor CXCR2 has been implied to play a substantial role in pathogenesis of atherosclerosis, but the underlying molecular mechanisms remain to be clarified. In the present study, we examined the modulating effect of oxLDL on expression of CXCR2 and its functional effect in monocytes. Methods and results: OxLDL (20-µg protein/ml), but not LDL (80-µg protein/ml), upregulated the surface expression of the CXC chemokine receptor CXCR2 (measured by flow cytometry) in both human freshly peripheral blood monocytes and human monocytic U937 cells. OxLDL, but not LDL, increased CXCR2 mRNA determined by RT-PCR in both cells. Treatment of oxLDL (40-µg protein/ml) enhanced chemotaxis of U937 cells to IL-8 and their adhesion to an endothelial cell line, ECV304 (both P<0.05 vs. control). Pretreatment of monocytes with scavenger receptor inhibitors, polyinosinic acid (100 µg/ml) and dextran sulfate (50 µg/ml) attenuated CXCR2 expression, but pertussis toxin or cholera toxin had no effect. OxLDL induced the activation of p38MAPK in monocytes, and this effect of oxLDL was blocked by the scanvenger receptor inhibitors. Furthermore, p38 MAPK inhibitors SB203580 or SK&F86002 markedly reduced oxLDL-induced CXCR2 expression. Conclusions: This observation demonstrated that oxLDL upregulates CXCR2 expression in monocytes and promotes the chemotaxis and adhesion of monocytes. The effect of oxLDL is mediated through scavenger receptor and p38 MAPK activation.

KEYWORDS Cytokines; Leukocytes; Lipoproteins; Receptors; Signal transduction


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