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


RESULTS
OxLDL (20-microg protein/ml), but not LDL (80-microg 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-microg 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 microg/ml) and dextran sulfate (50 microg/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.
Lei
Zhu Bin
ZB
Department of Cardiology, General Hospital of Jinan Military Area, Jinan 250031, China. leizhubin88@email.com.cn
Zhang
Zhe
Z
Jing
Qing
Q
Qin
Yong Wen
YW
Pei
Gang
G
Cao
Beng Zhen
BZ
Li
Xiao Yan
XY
D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D016264:Dextran Sulfate / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016209:Interleukin-8; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D011069:Poly I / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000187:drug effects; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013844:Thiazoles / Q000494:pharmacology; D020298:U937 Cells; D048051:p38 Mitogen-Activated Protein Kinases
D007093:Imidazoles; D016209:Interleukin-8; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011725:Pyridines; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D023063:Receptors, Interleukin-8B; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D013844:Thiazoles; C099252:oxidized low density lipoprotein; D011069:Poly I; D016264:Dextran Sulfate; C052026:6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580