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

doi:10.3877/cma.j.issn.1674-3253.2022.04.015

Abstract

Abstract:

Objective

To explore the effect and related mechanisms of PGE2 on lipopolysaccharide-induced inflammation of bladder epithelial cells.

Method

Normal human bladder epithelial cell (SV-HUC-1) were induced by lipopolysaccharide to establish a cystitis cell model, and real-time fluorescent quantitative PCR was used to detect the expression of EP4 receptor after the use of PGE2. With the treatment of EP4 receptor agonist and antagonist, MTT method was used to detect the effect on cell proliferation. Finally, the expression of IL-10, IL-6, IL-1β and TNF-α in cell culture medium were detected by ELISA method after the treatment of PGE2, EP4 receptor agonist and antagonist.

Results

PGE2 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-1β and 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.

Key words: Cystitis, PGE2, EP4 receptor, inflammatory response

Yihong Zhou, Yisong Lyu, Wenjie Cheng, Xiaoqing Zheng, Shuchang Huang, Minbo Yan, Yingbo Dai, Hao Zheng. PGE2 regulates lipopolysaccharide-induced inflammatory response in bladder epithelial cells by promoting EP4 receptor expression[J]. Chinese Journal of Endourology(Electronic Edition), 2022, 16(04): 351-355.

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References 27

[1]	张学宝，张其强，刘楚,等.腺性膀胱炎的诊疗进展[J/CD].中华腔镜泌尿外科杂志(电子版), 2019, 13(4): 271-274.
[2]	Hanno PM, Erickson D, Moldwin R, et al. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment [J]. J Urol, 2015, 193(5): 1545-4553.
[3]	Konya V, Marsche G, Schuligoi R, et al. E-type prostanoid receptor 4 (EP4) in disease and therapy [J]. Pharmacol Ther, 2013, 138(3): 485-502.
[4]	Lv YS, Yao YS, Rong L, et al. Intravesical hyaluronidase causes chronic cystitis in a rat model: a potential model of bladder pain syndrome/interstitial cystitis [J]. Int J Urol, 2014, 21(6): 601-607.
[5]	Trang LE. Prostaglandins and inflammation [J]. Seminars in Arthritis & Rheumatism, 2011, 9(3): 153-190.
[6]	Biswas S, Bhattacherjee P, Paterson CA, et al. Ocular inflammatory responses in the EP2 and EP4 receptor knockout mice [J]. Ocul Immunol Inflamm, 2006, 14(3):157-163.
[7]	Minami M, Shimizu K, Okamoto Y, et al. Prostaglandin E receptor type 4-associated protein interacts directly with NF-kappaB1 and attenuates macrophage activation [J]. J Biol Chem, 2008, 283(15): 9692-9703.
[8]	Lee J, Banu SK, Burghardt RC, et al. Selective inhibition of prostaglandin E2 receptors EP2 and EP4 inhibits adhesion of human endometriotic epithelial and stromal cells through suppression of integrin-mediated mechanisms [J]. Biol Reprod, 2013, 88(3): 77.
[9]	Mori A, Ito S, Morioka M, et al. Effects of specific prostanoid EP receptor agonists on cell proliferation and intracellular Ca(2+) concentrations in human airway smooth muscle cells [J]. Eur J Pharmacol, 2011, 659(1): 72-78.
[10]	Kundu N, Ma X, Kochel T, et al. Prostaglandin E receptor EP4 is a therapeutic target in breast cancer cells with stem-like properties [J]. Breast Cancer Res Treat, 2014, 143(1): 19-31.
[11]	Cabral M, Martín-Venegas R, Moreno JJ. Role of arachidonic acid metabolites on the control of non-differentiated intestinal epithelial cell growth [J]. Int J Biochem Cell Biol, 2013, 45(8): 1620-1628.
[12]	李江，周红庆，方克伟.膀胱尿路上皮屏障的功能及其在相关疾病中的研究进展[J].中华泌尿外科杂志, 2018, 39(7): 553-555.
[13]	Janssen D, van Wijk X, Jansen K, et al. The distribution and function of chondroitin sulfate and other sulfated glycosaminoglycans in the human bladder and their contribution to the protective bladder barrier [J]. J Urol, 2013, 189(1): 336-342.
[14]	吕夷松，荣禄，谢云,等.前列腺素E受体-4在透明质酸酶诱导大鼠慢性膀胱炎中的作用[J].中华实验外科杂志, 2013, 30(12): 2525-2527.
[15]	Alpizar Y, Uvin P, Naert R, et al. TRPV4 mediates acute bladder responses to bacterial lipopolysaccharides [J]. Front Immunol, 2020, 11: 799.
[16]	Wang X, Yin H, Fan L, et al. Shionone alleviates NLRP3 inflammasome mediated pyroptosis in interstitial cystitis injury [J]. Int Immunopharmacol. 2020, 90: 107132.
[17]	Wang X, Fan L, Yin H, et al. Protective effect of Aster tataricus extract on NLRP3-mediated pyroptosis of bladder urothelial cells [J]. J Cell Mol Med, 2020, 24(22): 13336-13345.
[18]	张晓音，吴旻，李雨萌, 等. 脂多糖的效应及其机理研究进展[J].动物医学进展, 2015, 36(12): 133-136.
[19]	位志峰，陈志强，叶章群.膀胱内灌注脂多糖法建立腺性膀胱炎动物模型的研究[J].临床泌尿外科杂志, 2006, 21(12): 933-934，937.
[20]	张伟，王东文.间质性膀胱炎/膀胱疼痛综合征膀胱黏膜组织中肥大细胞活化和相关免疫因子的表达及意义[J].中华泌尿外科杂志, 2018, 39(12): 900-904.
[21]	李华福，谢群，叶啸,等.肥大细胞应用于间质性膀胱炎/膀胱疼痛综合征特异性诊断Meta分析[J].国际泌尿系统杂志, 2018, 38(5): 771-775.
[22]	Omer K, Erdem A, Ismail TK, et al. Importance of TNF-related apoptosis-inducing ligand in pathogenesis of interstitial cystitis [J]. Int Urol Nephrol, 2010, 42(2): 393-399.
[23]	曲立娟，钟瑞华，卢颖莹,等. 宁泌泰胶囊对间质性膀胱炎大鼠炎性因子表达和激素水平的影响[J]. 上海中医药大学学报,2018, 32(3): 86-91.
[24]	Jung M, Ma Y, Iyer RP, et al. IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2 macrophage polarization and fibroblast activation [J]. Basic Res Cardiol, 2017, 112(3): 33.
[25]	Brockmann L, Soukou S, Steglich B, et al. Molecular and functional heterogeneity of IL-10-producing CD4⁺ T cells [J]. Nat Commun, 2018, 9(1): 5457.
[26]	Ip W, Hoshi N, Shouval D, et al. Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages [J]. Science, 2017, 356(6337): 513-519.
[27]	Yigitaslan S, Ozatik O, Ozatik F, et al. Effects of tadalafil on hemorrhagic cystitis and testicular dysfunction induced by cyclophosphamide in rats [J]. Urol Int, 2014, 93(1): 55-62.

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