The effects of ox-LDL in human atherosclerosis may be mediated in part via the toll-like receptor 4 pathway.
Toll-like receptor 4 (TLR4) may provide a potential pathophysiological link between lipids and infection/inflammation and atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) makes it more atherogenic than its native form. The purpose of the study was to investigate the relationship between the effects of ox-LDL in human atherosclerosis and the expression of TLR4. We studied the relationship between TLR4 and ox-LDL, pro and con, using both real-time quantitative RT-PCR and RNA interference technology through in vitro cell culture. Nuclear factor kappa B (NF-kappa B) activity and the concentrations of monocyte chemoattractant protein-1(MCP-1) and interleukin-8 (IL-8) were detected by ELISA. The results showed that the expression of TLR4 increased in response to ox-LDL. Simultaneously, NF-kappa B relative activity and the concentrations of MCP-1 and IL-8 in cell supernatant were upregulated by ox-LDL in a dose-dependent manner. TLR4 expression was inhibited by small interference RNA(siRNA) plasmid expression vectors; NF-kappa B activity and the secretions of MCP-1 and IL-8 in response to ox-LDL were significantly lower in the group wherein TLR4 expression has been inhibited than that in the group wherein TLR4 expression has not been inhibited. We suggest that the atherogenic effects of ox-LDL could be mediated in part via the TLR4 pathway. Furthermore, inhibition of TLR4 expression may downregulate the NF-kappa B activity and secretions of MCP-1 and IL-8 in monocytes due to oxidized LDL, resulting in the alleviation of the progress of atherosclerosis.
Geng
Honglian
H
Department of Laboratory Diagnosis, Changzheng Hospital, Second Military Medical University, Shanghai, China. hlgeng@yahoo.com.cn
Wang
Aihua
A
Rong
Guanghua
G
Zhu
Bei
B
Deng
Yan
Y
Chen
Jun
J
Zhong
Renqian
R
D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells
D018932:Chemokine CCL2; D016209:Interleukin-8; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C099252:oxidized low density lipoprotein
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