title: NF-kB activity-dependent P-selectin involved in ox-LDL-induced foam cell formation in U937 cell.
abstract: Oxidized low-density lipoprotein (ox-LDL) plays a critical role in regulation of atherosclerosis. However, little is known about the role of Nuclear factor kB (NF-kB) activity-dependent P-selectin in ox-LDL-induced foam cell formation during atherosclerosis. In this study, we first investigated ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. Treatment of U937 cells with ox-LDL increased lipid accumulation as well as intracellular cholesterol content. Next, a comparative analysis of gene expression profiling using cDNA microarray and Real-time-PCR indicated that ox-LDL exposure induced, in three treated groups, an extremely marked increase in the mRNA level of P-selectin. Protein levels of P-selectin and its upstream regulators IkBa and NF-kB showed that NF-kB pathway is involved in the ox-LDL-induced foam cell formation. Finally, overexpression of NF-kB significantly accelerated, whereas, inhibition of NF-kB with siRNA remarkably attenuated ox-LDL-induced macrophage-derived foam cell formation. It was concluded that the activity of NF-kB is augmented during macrophage-derived foam cell formation. Activation of NF-kB increased, whereas, inhibition of NF-kB decreased ox-LDL-induced P-selectin expression and lipid accumulation in macrophages, suggesting ox-LDL induced expression of P-selectin through degradation of IkBa and activation of NF-kB in the regulation of foam cell formation.
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China. wangyi2004a@126.com
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Minghui
authors.initials: M
authors.lastname: Sun
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Heng
authors.initials: H
authors.lastname: Cao
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
mesh_terms: D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells
chemical_list: D008077:Lipoproteins, LDL; D016328:NF-kappa B; D019007:P-Selectin; C099252:oxidized low density lipoprotein