油酰乙醇胺对脂多糖诱导的THP-1细胞炎症因子表达的影响

目的探讨油酰乙醇胺(OEA)对细菌脂多糖(LPS)诱导的人急性白血病单核细胞(THP-1)中前炎症因子TNF-α、IL-1β、IL-6表达的影响,并初步探讨OEA作为过氧化物酶体增殖物激活受体-α(PPAR-α)激动剂参与对炎症调节的作用机制。方法体外培养的THP-1细胞,分别加入不同浓度的OEA(10,20,40μmol/L)或非诺贝特(100μmol/L)共同孵育1 h后,用1μg/mL LPS分别诱导6或24 h。采用RT-PCR、实时定量PCR和酶联免疫吸附检测测定细胞中TNF-α、IL-1β、IL-6 mRNA和蛋白的表达的变化,并使用实时定量PCR及Western blot方法检测PPAR-α及Toll样受体4(TLR4)的mRNA和蛋白的表达。结果相对于正常THP-1细胞,LPS诱导后细胞中炎症因子(TNF-α、IL-1β、IL-6)表达明显增加。OEA对TNF-α、IL-1β、IL-6 mRNA和蛋白的表达有抑制作用,并呈现出一定的剂量依赖性。且OEA在激活PPAR-α表达的同时能够抑制TLR4的表达。结论 OEA对LPS诱导的炎症反应有抑制作用,其机制可能与激活PPAR-α,下调TLR4的表达有关。

The effect of oleoylethanolamide on the expression of cytokines in lipopolysaccharide induced THP-1 cells

Purpose To investigate the effect of oleyletheanolamide(OEA) on the expression of proinflammatory cytokines TNF-α,IL-1β,and IL-6 in lipopolysaccharide(LPS) induced THP-1 cells and its mechanism.MethodsTHP-1 cells were pretreated with different concentrations of OEA(10,20,40 μmol/L)or fenofibrate(100 μmol/L) for 1 h,before stimulated with 1 μg/mL LPS for another 6 h or 24 h.The expression of cytokines was detected by RT-PCR,Real-time PCR and Cell Enzyme linked immunosorbent assay.Real-time PCR and western blot were performed to measure the expression of PPAR-α and Toll like receptor 4(TLR4) in mRNA and protein levels.ResultsOEA inhibited the expression of LPS induced TNF-α,IL-1β,IL-6 at mRNA and protein levels and markedly up-regulated PPAR-α,as well as inhibited the expression of TLR4 in the LPS induced THP-1 cells.ConclusionOEA could inhibited the inflammation of monocytes response to the stimulation of LPS,which may be related to the activation of PPAR-α and down-regulation of the expression of TLR4.