Knockdown RIP-1 inhibits production of oxLDL-induced inflammatory cytokines and promotes ABCA1 expression in macrophages

Background and objective: Accumulation of oxidized cholesterol in macrophages is a key factor to initiate and accelerate atherosclerosis. In the present study, we investigated the role of receptor-interacting serine/threonine-protein kinase 1 (RIP-1, RIPK1) in the progression of oxidized low-density lipoprotein (ox-LDL)-induced inflammation of macrophages and the cholesterol transport outside of the macrophages. Methods: RAW264.7 cells were treated with increasing concentrations of oxLDL for indicated time. Inflammatory cytokines secretion was determined by ELISA assay. The levels of NF-kappa B p65, I kappa B alpha, RIP-1, TRAF3 and IKK alpha were determined by Western blotting analysis. Results: oxLDL induced inflammatory cytokines production in a time-and dose-dependent manner. The ox-LDL-induced cytokines production were mediated by NF-kappa B pathways in macrophage cells. oxLDL treatment upregulated the RIP-1 expression in RWA264.7 cells and interference with RIP-1 decreased the secretion of TNF-alpha and IL-6. Moreover, knockdown RIP-1 increased the ABCA1 levels in RAW264.7 cells. Conclusion: oxLDL promoted the expression of RIP-1 in RAW264.7 cells. Knockdown RIP-1 in macrophages decreased the inflammatory cytokines production and promoted the expression of ABCA1. Thus, inhibiting the level of RIP1 might be useful to suppress the chronic inflammatory response and promote the reverse transport of cholesterol in development of atherosclerosis.