Premium
Hydrostatic pressure and muscarinic receptors are involved in the release of inflammatory cytokines in human bladder smooth muscle cells
Author(s) -
Liang Zhou,
Xin Wei,
Qiang Liu,
Xiang Cai,
BangHua Liao,
Jin Yang,
DeYi Luo,
Hong Li,
KunJie Wang
Publication year - 2017
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.23104
Subject(s) - muscarinic acetylcholine receptor , hydrostatic pressure , receptor , proinflammatory cytokine , muscarinic acetylcholine receptor m3 , endocrinology , medicine , inflammation , acetylcholine , atropine , muscarinic acetylcholine receptor m1 , physics , thermodynamics
Aims Abnormal 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). Methods Animal 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. Results In obstructed bladder, inflammatory genes and macrophage infiltration were remarkably induced. When HBSMCs were subjected to 200–300 cm H 2 O 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. Conclusions Hydrostatic 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.