Hydrostatic pressure and muscarinic receptors are involved in the release of inflammatory cytokines in human bladder smooth muscle cells.
Hydrostatic pressure and muscarinic receptors are involved in the release of inflammatory cytokines in human bladder smooth muscle cells.
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静水压和毒蕈碱受体参与人膀胱平滑肌细胞中炎症细胞因子的释放。
DOI：
10.1002/nau.23104
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Kun-Jie Wang
中科院分区：
文献类型：
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作者：
Liang Zhou;Xin Wei;Qiang Liu;Xiang Cai;Bang-Hua Liao;Jin Yang;De-Yi Luo;Hong Li;Kun-Jie Wang
目的膀胱内压力异常会导致一系列的病理改变。研究静水压力和M受体对大鼠和人膀胱平滑肌细胞(HBSMCs)释放炎性细胞因子的影响。高静水压和/或乙酰胆碱(Ach)作用于HBSMC。免疫组织化学染色检测膀胱壁巨噬细胞的浸润情况。结果梗阻性膀胱炎性基因表达明显增强，巨噬细胞明显增多。当HBSMC在2 0 0~30 0 cm H2O压力作用2~2 4 h时，IL-6和RANTES的表达显著增加。静液压可促进磷酸化NFERKBp65、κ1/2及M受体的蛋白表达。此外，NFκB或ERK1/2抑制剂可抑制压力诱导的炎症基因的表达。1 μM乙酰胆碱处理细胞6 h后，IL-6m RNA表达显著增加。乙酰胆碱还可增强压力诱导的磷酸化核因子κB p65和IL-6蛋白表达。结论静水压力和M受体参与了炎症细胞因子的分泌，提示静水压力和M受体在BOO的病理过程中具有促炎作用。
AimsAbnormal intravesical pressure results in a series of pathological changes. We investigated the effects of hydrostatic pressure and muscarinic receptors on the release of inflammatory cytokines in rat and human bladder smooth muscle cells (HBSMCs).MethodsAnimal model of bladder outlet obstruction was induced by urethra ligation. HBSMCs were subjected to elevated hydrostatic pressure and/or acetylcholine (Ach). Macrophage infiltration in the bladder wall was determined by immunohistochemical staining. The expression of inflammatory genes was measured by RT‐PCR, ELISA and immunofluorescence.ResultsIn obstructed bladder, inflammatory genes and macrophage infiltration were remarkably induced. When HBSMCs were subjected to 200–300 cm H2O pressure for 2–24 h in vitro, the expressions of IL‐6 and RANTES were significantly increased. Hydrostatic pressure promoted the protein levels of phospho‐NFκB p65 and phospho‐ERK1/2 as well as muscarinic receptors. Moreover, NFκB or ERK1/2 inhibitors suppressed pressure‐induced inflammatory genes mRNA. When cells were treated with 1 μM acetylcholine for 6 h, a significant increase in IL‐6 mRNA expression was detected. Acetylcholine also enhanced pressure‐induced phospho‐NFκB p65 and IL‐6 protein expression. Additionally, pressure‐induced IL‐6 was partially suppressed by muscarinic receptors antagonists.ConclusionsHydrostatic pressure and muscarinic receptors were involved in the secretion of inflammatory cytokines in HBSMCs, indicating a pro‐inflammatory effect of the two factors in the pathological process of BOO.