雷公藤甲素抑制外周血单个核细胞分泌IL-1β及其基因多态性的关系

The correlation of the inhibitory effect of triptolide on interleukin-1βproduction from peripheral blood mononuclear cells with the gene polymorphisms of interleukin-1β

目的探讨雷公藤甲素抑制外周血单个核细胞(PBMC)分泌白细胞介素-1β(IL-1β)及其基因多态性的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法,对31名健康志愿者IL-1β基因启动子区-511位点C-T多态性进行基因型检测,同时进行PBMC培养,用脂多糖(LPS)刺激培养细胞,并予以雷公藤甲素处理PBMC,收集培养上清液,酶联免疫吸附试验(ELISA)检测上清液中IL-1β的含量。结果携带IL-1β-511T/T纯合子基因型PBMC经LPS刺激后,IL-1β的分泌量明显较非T/T纯合子为高(P<0.05);雷公藤甲素能显著抑制LPS诱导的C/C和C/T基因型PBMC分泌IL-1β(P<0.05),但对T/T基因型的抑制作用不明显(P>0.05)。结论IL-1β基因-511C-T多态性与IL-1β的分泌量相关,雷公藤甲素对不同基因型的IL-1β抑制作用有差异,这可能是导致雷公藤药理作用出现个体差异的原因之一。

Objective To explore whether interleukin （IL）-1β gene polymorphisms is associated with the inhibitory effect of triptolide nn IL-1β production from peripheral blood mononuelear cells（PBMC）. Methods IL-1β gene pnlymorphism was analyzed in 31 healthy volunteers. From genomic DNA, the C-T polymorphism at IL-1β-511 was typed by PCR-RFLP. Meanwhile the IL-1β wax also measured in the supernatant of the cultured and stimulated PBMC by ELISA. Results The PBMC cultures of healthy subjects were stimulated by LPS. the seeretion levels of IL-1β in 9 volunteers who carried IL-1β-511 T/T genotype were higher than volunteers who carried no T/T genotypes （P〈0.05）. Triptolide suppressed significantly the production of IL-1β from LPS treated human PBMC carried C/C and C/T genotype （P〈0.05）. but this significant inhibitory effect of triptolide was not observed in T/T genotype （P〉0.05）. Conclusion The gene polymorphism at IL-1β-511 affects the secretion of IL-1β, but the inhibitory effect of triptolide on the production of IL-1β is different in C/ C. C/T. T/T genotype of IL-1β-511. which may be one of the reasons that the that therapy responses to triptolide are diffcrent in different individuals.