C‐reactive protein upregulates lectin‐like oxidized LDL receptor‐1 expression in THP‐1‐derived macrophages through NF‐κB

Abstract

Lectin-like oxidized LDL receptor-1 (LOX-1), a newly identified scavenger receptor, has been increasingly linked to atherosclerosis. C-reactive protein (CRP), a prototypic inflammatory marker, has been proven to promote atherogenesis. In this study, we evaluated the in vitro effects of CRP on LOX-1 expression and the associated signal transduction pathway in THP-1-derived macrophages. Our study showed that incubation of macrophages with CRP significantly enhanced expression of LOX-1 protein and mRNA levels in macrophages in a dose-dependent manner; this expression could be suppressed by the nuclear factor kappa B (NF-κB) pathway inhibitor BAY11-7085. However, LOX-1 was not inhibited by the inhibitor of mitogen-activated protein kinase (MAPK) proteins (SP600125-JNK/SAPK, SB203580-p38, and U0126-ERK1/2) in macrophages. In conclusion, human native CRP up-regulated LOX-1 expression in THP-1-derived macrophages primarily through the NF-κB signaling pathway. Practical applications: Identification of LOX-1 and definition of its biological role in pathophysiological states provided a new clue for understanding the nature of oxLDL uptake into macrophages. Internalization of modified lipoprotein by macrophages and foam cell formation are critical events in hypertension, diabetes mellitus, and dyslipidemia, which are the most important risk factors for atherosclerosis. As a characteristic inflammatory marker, CRP has been proven to play a pivotal role in promoting atherogenesis. However, crosstalk between CRP and LOX-1 on macrophages has not been elucidated. Therefore, determining the regulatory process for LOX-1 and the underlying signal transduction pathways may provide a new insight into the mechanism of atherosclerosis.