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 infl ammatory 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-αnd further treated with CRP in the absence or presence of specifi c inhibitors or small interfering RNA (siRNA). Our results showed that CRP increased sLOX-1 release from activated macrophages in a dosedependent manner and that these effects were regulated by Fc γ receptor II (Fc γ RII)-mediated p47phox 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 Fc γ RII or with CD32 siRNA, p47phox 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 Fc γ RIImediated p47 phox phosphorylation, ROS production, and TACE activation. CRP enhances soluble LOX-1 release from macrophages by activating TNF- α converting enzyme. © 2011 by the American Society for Biochemistry and Molecular Biology, Inc. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc.