PGE2通过促进EP4受体表达调控脂多糖诱导的膀胱上皮细胞炎症反应

PGE2 regulates lipopolysaccharide-induced inflammatory response in bladder epithelial cells by promoting EP4 receptor expression

目的:探讨PGE2对脂多糖诱导的膀胱上皮细胞炎症反应的影响及相关机制。方法:利用脂多糖诱导人正常膀胱上皮细胞(SV-HUC-1)建立膀胱炎细胞模型,采用实时荧光定量PCR检测PGE2作用后膀胱上皮细胞中EP4受体的表达水平变化。利用EP4受体激动剂和拮抗剂作用于膀胱上皮细胞,MTT方法检测其对细胞增殖的影响。最后分别利用PGE2及EP4受体激动剂、拮抗剂作用于膀胱上皮细胞,ELISA方法检测细胞培养液中IL-10、IL-6、IL-1β和TNF-α的变化。结果:PGE2促进膀胱上皮细胞中EP4受体的表达,并呈时间依赖。EP4受体激动剂(CAY10598)促进膀胱上皮细胞的细胞增殖,而EP4受体拮抗剂(AH23848)抑制细胞增殖(P<0.05)。ELISA法检测发现,PGE2和CAY10598能促进膀胱上皮细胞培养液中IL-10、IL-6、IL-1β和TNF-α等炎症因子的表达,而AH23848则起到抑制作用(P<0.05)。结论:PGE2通过上调EP4受体表达促进脂多糖诱导的膀胱上皮细胞炎症反应,PGE2/EP4受体有望是膀胱炎治疗的潜在靶点。

Objective To explore the effect and related mechanisms of PGE2 on lipopolysaccharide-induced inflammation of bladder epithelial cells.MethodNormal human bladder epithelial cell(SV-HUC-1)were induced by lipopolysaccharide to establish a cysttis cell model,and realtime fuorescent quantitative PCR was used to detect the expression of EP4 receptor after the use of PGE2.With the treatment ofEP4 receptor agonist and antagonist,MTTmethod was used to detect the eect on cel proliferation.Finally,the expression ofIL-I0,IL-6,IL-Iβand TNF-ain cell culture medium were detected by ELISAmethod after the treatment of PGE2,EP4 receptor agonist and antagonist.ResultsPGE2 promoted the expression of EP4 receptor in bladder epithelial cell.EP4 receptor agonist(CAY10598)promoted cell proliferation,while EP4 receptor antagonist(AH23848)inhibited cell proliferation(P<0.05).Furthermore,PGE2 and CAY10598 promoted the expression of IL-10,IL-6,IL-1βand TNF-α,while AH23848 had an inhibitory effect(P<0.05).Conclusion PGE2 promotes lipopolysaccharide-induced inflammatory response in bladder epithelial cells by up-regulating the expression of EP4 receptor.And PGE2/EP4 receptor is expected to be a potential target for the treatment of cystitis.