PPARγ不同配体对LPS诱导人滋养细胞炎症细胞因子的调节

The regulation of PPARγ ligands on LPS-induced inflammatory cytokine in human trophoblast.

目的:探讨PPARγ的天然激动配体15-d-PGJ2和合成配体Troglitazone对人滋养细胞IL-6、IL-8和TNF-α分泌的调节及其可能的机制。方法:以LPS刺激体外培养的滋养细胞作为炎症细胞模型,细胞经10mg/L的LPS与30μmol/L的15-d-PGJ2和Tro-glitazone单独或联合处理,培养6h后收集上清,通过ELISA定量检测IL-6、IL-8和TNF-α的分泌,通过Western blot检测处理后细胞NF-B蛋白活性的变化。结果:滋养细胞经15-d-PGJ2和Troglitazone处理后,LPS诱导的IL-6、IL-8和TNF-α分泌,分别下降97.53%,93.10%,90.62%和92.68%,73.85%,91.80%,差异均有显著统计学意义(P<0.05),且15-d-PGJ2可抑制NF-B蛋白活性,而Troglitazone无此作用。结论:PPARγ被配体激活后可调节人滋养细胞炎症细胞因子的分泌,部分机制可能是通过抑制NF-B蛋白活性实现的,因此,从平衡炎症反应角度为预防和治疗子痫前期提供了实验依据。

Objective：To investigate the regulation of natural ligand 15-deoxy-△12, 14PGJ2 （15-d-PGJ2） and synthetic ligand Troglitazone of PPARγ on the secretion of IL-6, IL- 8, and TNF-α from cultured human trophoblast and its possible mechanism. Methods：Based on cell culture technology, cultured thophoblast stimulated with LPS in vitro as inflammatory cell model was performed, cells incubated in the presence of 10mg/L lipopolysaccharide （LPS） in the absence or presence of 30umol/L 15-d-PGJ2 or troglitazone. After a 6hour incubation, the incubation medium was collected and the release of IL-6, IL-8, and TNF-α was quantified by ELISA. Cell was collected and protein activity of NF- B was detected by Western blot. Results： Treatment of trophoblast with both 15d-PGJ2 and troglitazone significantly reduced the release of LPS-stimulated IL-6, IL-8, and TNF-α （ P 〈 0.05 ）, which were 97.53% ,93.10% ,90. 62% and 92.68% ,73.85% ,91.80% respectively. Western blot demonstrated that 15-d-PGJ2, but not troglitazone, suppressed protein activity of NF- B. Conclusion： The data present in this study demonstrate that the formation of proinflammatory mediators can be modulated by currently available PPARα ligands, and its mechanism in part caused by antagonizing the protein activities of the NF- B. Therefore, in the view of balance of inflammatory reaction, present experiment provides evidence for prevention and treatment of preeclampsia.