肝X受体激动剂T0901317对脂多糖诱导的THP-1巨噬细胞炎性因子释放的影响及其机制  

Effect and Mechanisms of Liver X Receptor Agonist T0901317 on Release of Proinflammatory Cytokines from THP-1 Macrophage Induced by Lipopolysaccharides

作　　者：赵国军[1,2] 汤石林[1,3] 田国平[1,4] 欧阳新平[1] 吕运成[1] 何平平[1,5] 姚峰[1] 唐艳艳[1] 吴剑锋[1] 王甲林[1] 张敏[1] 唐朝克[1] 

机构地区：[1]南华大学心血管疾病研究所生命科学研究中心动脉硬化湖南省重点实验室 [2]南华大学组织学与胚胎学教研室 [3]南华大学附属第一医院ICU [4]南华大学附属第二医院心内科 [5]南华大学护理学院,湖南省衡阳市421001

出　　处：《中国动脉硬化杂志》2013年第7期594-598,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(81200218;81170278和81070220)资助;衡阳市科技局课题(2011KJ11)

摘　　要：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。Aim T0901317 is a synthetic liver X receptor （LXR） agonist. This study was to investigate the effects and potential mechanisms of T0901317 on proinflammatory cytokine release from lipopolysaccharide （LPS）-induced THP-1 macrophages. Methods Human THP-1 macrophages were induced using phorbol-12-myristate acetate （PMA, 160 nmol/L） for 24 h, then cells were divided into four groups： control group, LPS group, T0901317 group and LPS＋T0901317 group. Secretion of proinflammatory cytokines, including tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） and interleukin-1β （IL-1β） was performed by enzyme-linked immunosorbent assay （ELISA）. The siRNAs for ATP-binding cassette transporter A1 （ABCA1） were transfected into THP-1 macrophages by positive ion liposome LipofectamineTM2000. The mRNA expression of ABCA1, ABCG1 and Toll like receptor 4 （TLR4） were examined by real-time PCR analysis. The proteins expression of ABCA1, ABCG1, TLR4 and nuclear factor-κB （NF-κB） p65 were examined by Western blot. Results T0901317 inhibited the release of TNF-α, IL-6 and IL-1β induced by LPS, and promoted the expression of ABCA1 and ABCG1 on THP-1 macrophages. Transfection of ABCA1 siRNA significantly decreased the of expression ABCA1 protein and weakened the effect of T0901317 on the LPS-stimulated inflammatory response. Furthermore, T0901317 repressed the expression of TLR4 and the translocation of NF-κB to the nucleus. Conclusions T0901317 inhibited the release of inflammatory cytokine that induced by LPS, and the mechanisms may be related to promotion of membrane transporter ABCA1 expression and inhibition of membrane receptors TLR4 and the transcription factor NF-κB expression.

关 键 词：肝X受体 T0901317 ATP结合盒转运子A1 Toll样受体4 核因子ΚB 动脉粥样硬化 

分 类 号：R363[医药卫生—病理学]