蜕皮甾酮对口腔扁平苔藓上皮细胞TLRs/NF-κB信号通路的调节作用

Effects of ecdysterone on toll-like receptors/nuclear factor kappaB signaling pathway in the epithelial cells of oral lichen plus

目的:研究Toll样受体/核转录因子-κB(TLRs/NF-κB)信号通路在口腔扁平苔藓(oral lichen plus,OLP)病理过程中的作用,探讨蜕皮甾酮(ecdysterone,EDS)在OLP治疗中的作用效应。方法:(1)脂多糖(LPS)刺激人口腔黏膜角质形成细胞(HOK)建立体外OLP炎症模型,采用Real time RTPCR检测NF-κB p65、TLR4和肿瘤坏死因子-a(TNF-α)mRNA在该模型中的表达情况;(2)EDS干预HOK细胞后,RT-PCR检测NF-κB p65、TLR4和TNF-αmRNA的表达情况。结果:体外OLP炎症模型中NF-κB p65、TLR4和TNF-αmRNA表达量上调,且呈LPS浓度及作用时间依赖性,LPS浓度为10μg/mL,作用6h时表达量最高。EDS能够下调NF-κB p65、TLR4和TNF-αmRNA的表达,EDS最佳作用浓度是100μg/mL(P<0.01)。结论:EDS对OLP的抗炎及免疫调节作用与TLRs/NF-κB信号通路密切相关,EDS可能通过抑制TLRs的激活,调控NF-κB的表达,最终抑制OLP炎症介质活化与黏膜损伤。

Objective. To explore the role of TLRs/NF-B signaling pathway in oral lichen plus （OLP）, and the effect of ecdysterone （EDS） on OLP. Methods： OLP inflammation model in vitro was es- tablished by stimulating HOK cells, and the levels of NF-B p65, TLR4 and TNF-am RNA expression were determined by Real time RT-PCR. LPS-induced NF-,：B p65, TLR4 and TNF- mRNA expression in irt-vitro-cultured OLP model was determined by RT-PCR before and after the treatment of EDS. Results： In in-vitro-cultured OLP model, NF-：Bp65, TLR4 were expressed spondaneously, and the expression ofNF-B p65, TLR4 and TNF-a mRNA was significantly upregnlated after the treatment of LPS with 10 g/ mL final concentration and for 6 h. EDS could distinctively downregulated the expression of NF-B p65, TLR4 and TNF-a mRNA induced by LPS ,and the effect of EDS was strongest with 100 #g/mL final con- centration （P0.01）. Conclusions.TLRs/NF-：B signaling pathway may attributed to the immune patho- genesis of OLP EDS may interfere the activation of NF-B by specifically inhibiting the expression of TLRs, and finally inhibiting the inflammatory mediators＂ activity and mucosal damage.