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目的观察肝X受体激动剂T0901317对脂多糖诱导的THP-1巨噬细胞炎症因子释放的影响,并探讨其机制。方法 160 nmol/L佛波酯孵育THP-1巨噬细胞24 h后分为四组:对照组、脂多糖组、T0901317组和脂多糖+T0901317组,酶联免疫吸附法检测培养液中炎症因子含量。LipofectamineTM2000转染ATP结合盒转运子A1(ABCA1)siRNA,定量PCR检测细胞ABCA1、ABCG1和Toll样受体4(TLR4)的mRNA表达,Western blot检测AB-CA1、ABCG1、TLR4和核因子κB(NF-κB)p65的蛋白表达。结果 T0901317抑制脂多糖诱导的肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)和白细胞介素1β(IL-1β)释放,促进THP-1巨噬细胞ABCA1和ABCG1表达;转染ABCA1 siRNA后,ABCA1的蛋白表达明显下降,T0901317对炎症因子的抑制作用明显减弱;T0901317下调TLR4和核内NF-κB的表达。结论 T0901317抑制脂多糖诱导的炎症反应,可能与其促进膜转运体ABCA1表达,抑制膜受体TLR4和转录因子NF-κB的表达有关。
Objective To observe the effect of hepatic X receptor agonist T0901317 on the release of inflammatory factors of THP-1 macrophages induced by lipopolysaccharide and its mechanism. Methods THP-1 macrophages were incubated with phorbol ester at 160 nmol / L for 24 h and then divided into four groups: control group, lipopolysaccharide group, T0901317 group and lipopolysaccharide plus T0901317 group. The levels of inflammatory cytokines content. The expression of ABCA1, ABCG1 and Toll-like receptor 4 (TLR4) mRNA in ABCA1 cells was detected by LipofectamineTM2000. The expressions of AB-CA1, ABCG1, TLR4 and NF- -κB) p65 protein expression. Results T0901317 could inhibit the release of TNF-α, IL-6 and IL-1β induced by lipopolysaccharide and promote the expression of ABCA1 and ABCG1 in THP-1 macrophages. ABCA1 siRNA transfected ABCA1 protein decreased significantly, T0901317 significantly reduced the inhibition of inflammatory cytokines; T0901317 downregulated the expression of TLR4 and nuclear NF-κB. Conclusion T0901317 inhibits the inflammatory response induced by lipopolysaccharide, which may be related to the promotion of ABCA1, the membrane receptor TLR4 and the transcription factor NF-κB.