title: [Inhibitory effects of fluvastatin on activation of THP-1 cells induced by anti-beta2GPI/beta2GPI complex].
abstract: This study is to explore the interventional effects of fluvastatin on anti-beta2GPI/beta2GPI-induced activation in THP-1 mononuclear cells. In vitro, human mononuclear cells THP-1 were treated with fluvastatin, LPS and anti-beta2GPI/beta2GPI, then the TF expression on THP-1 cells was detected by real-time quantitative PCR (RT-qPCR) or TF activity was detected by kit. TNF-alpha mRNA and its protein expression were investigated by RT-PCR and ELISA kit. The expression of phospho-NF-kappaB p65 and inhibitory protein of NF-kappaB (IkappaB-alpha) were measured by Western blotting. The results suggested that the expression of TF and TNF-alpha on THP-1 cells was significantly up-regulated with treatment of anti-beta2GPI/beta2GPI complex (100 mg x L(-1)), compared with that of untreated cells (P < 0.05). Fluvastatin (50 mg x L(-1)) could decrease TF (mRNA and activity) expression and the level of TNF-alpha (mRNA and protein) in THP-1 cells with anti-beta2GPI/beta2GPI complex. The expression of TF and TNF-alpha was shown in a concentration-dependent manner. Moreover, anti-beta2GPI/beta2GPI complex could downregulate IkappaB-alpha levels and increase the levels of phospho-NF-kappaB p65. And these effects of anti-beta2GPI/beta2GPI complex could be blocked by fluvastatin. In conclusion, fluvastatin may interfere the expression and regulation of NF-kappaB signal transduction pathway, thereby inhibit the effects of anti-beta2GPI/beta2GPI on activation of THP-1 cells, by decreasing the expression of TF and TNF-alpha.
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Xie
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Long-Fei
authors.initials: LF
authors.lastname: Xia
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Mu
mesh_terms: D000936:Antigen-Antibody Complex / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000378:metabolism; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D053482:beta 2-Glycoprotein I / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020672:I-kappa B Proteins; D007211:Indoles; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D053482:beta 2-Glycoprotein I; D000072000:NF-KappaB Inhibitor alpha; D000077340:Fluvastatin; D013925:Thromboplastin