Curcumin affects ox-LDL-induced IL-6, TNF-?, MCP-1 secretion and cholesterol efflux in THP-1 cells by suppressing the TLR4/NF-?B/miR33a signaling pathway.
ABSTRACT: The aim of the present study was to study the molecular mechanism of how curcumin decreases the formation of ox-LDL induced human monocyte macrophage foam cells, promotes the efflux of cholesterol and reduces the secretion of inflammatory cytokines. In vitro cultured THP-1 cells were induced to become macrophages using phorbol-12-myristate-13-acetate. The cells were then pre-treated with curcumin before inducing the foam cell model by addition of oxidized low-density lipoprotein (ox-LDL). Western blot assays were used to detect expression levels of toll-like receptor (TLR)4, nuclear factor ?B (NF-?B), NF-?B inhibitor ? (I?B?), phosphorylated-I?B? and ATP binding cassette transporter (ABC)A1. Reverse transcription-quantitative PCR was employed to examine mRNA levels of TLR4, microRNA (miR)33a and ABCA1. ELISAs were used to detect inflammatory factors, including tumor necrosis factor (TNF)-?, monocyte chemotactic protein (MCP)-1 and interleukin (IL)-6. ox-LDL successfully induced the foam cell model, promoted phosphorylation of I?B?, promoted nuclear translocation of NF-?B, promoted the expression of TLR4 and miR33a, and promoted the secretion of TNF-?, MCP-1 and Il-6. Additionally, ox-LDL reduced the expression of ABCA1 and cholesterol efflux. However, pretreatment with curcumin increased the expression of ABCA1 and cholesterol efflux and suppressed secretion of TNF-?, MCP-1 and Il-6. TLR4 antibodies, the NF-?B blocker, PDTC, and the miR33a inhibitor also reduced the abnormal transformations induced by ox-LDL. Curcumin promoted cholesterol efflux by suppressing the TLR4/NF-?B/miR33a signaling pathway, and reduced the formation of foam cells and the secretion of inflammatory factors.