title: CRP enhances soluble LOX-1 release from macrophages by activating TNF-α converting enzyme.
abstract: Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) play an important role in the development and progression of atherosclerosis. We hypothesized that the inflammatory marker C-reactive protein (CRP) might stimulate sLOX-1 release by activating tumor necrosis factor-α converting enzyme (TACE). Macrophages differentiated from THP-1 cells were stimulated with TNF-α and further treated with CRP in the absence or presence of specific inhibitors or small interfering RNA (siRNA). Our results showed that CRP increased sLOX-1 release from activated macrophages in a dose-dependent manner and that these effects were regulated by Fc γ receptor II (FcγRII)-mediated p47(phox) phosphorylation, reactive oxygen species (ROS) production, and TACE activation. CRP also enhanced sLOX-1 release from macrophages derived from peripheral blood mononuclear cells (PBMC) of patients with acute coronary syndrome (ACS). Pretreatment with antibody against FcγRII or with CD32 siRNA, p47(phox) siRNA, apocynin, N-acetylcysteine, tumor necrosis factor-α protease inhibitor 1 (TAPI-1) or TACE siRNA attenuated sLOX-1 release induced by CRP. CRP also elevated serum sLOX-1 levels in a rabbit model of atherosclerosis. Thus, CRP might stimulate sLOX-1 release, and the underlying mechanisms possibly involved FcγRII-mediated p47(phox) phosphorylation, ROS production, and TACE activation.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
authors.forename: Xue Qiang
authors.initials: XQ
authors.lastname: Zhao
authors.forename: Ming Wei
authors.initials: MW
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Yu Xia
authors.initials: YX
authors.lastname: Zhao
authors.forename: Jing Jing
authors.initials: JJ
authors.lastname: Li
authors.forename: Xu Ping
authors.initials: XP
authors.lastname: Wang
authors.forename: Pei Li
authors.initials: PL
authors.lastname: Bu
authors.forename: Jian Min
authors.initials: JM
authors.lastname: Yang
authors.forename: Xiao Ling
authors.initials: XL
authors.lastname: Liu
authors.forename: Ming Xiang
authors.initials: MX
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D011817:Rabbits; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C495137:OLR1 protein, human; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human