title: Hydrostatic pressure and muscarinic receptors are involved in the release of inflammatory cytokines in human bladder smooth muscle cells.
abstract: OBJECTIVE
  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 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.
  
  
  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.
authors: Department of Urology, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors: Zhou
authors: Z
authors: Liang
authors: Department of Urology, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors: Wei
authors: W
authors: Xin
authors: Department of Urology, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors: Liu
authors: L
authors: Qiang
authors: Department of Urology, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors: Cai
authors: C
authors: Xiang
authors: Department of Urology, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors: Liao
authors: L
authors: Bang-Hua
authors: Department of Urology, Affiliated Hospital/Clinical Medical College of Chengdu University, Chengdu, P.R. China.
authors: Yang
authors: Y
authors: Jin
authors: Department of Urology, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors: Luo
authors: L
authors: De-Yi
authors: Department of Urology, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors: Li
authors: L
authors: Hong
authors: Department of Urology, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors: Wang
authors: W
authors: Kun-Jie
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004194:Disease; D005260:Female; D006801:Humans; D006874:Hydrostatic Pressure; D018727:Muscarinic Antagonists / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D051996:Transcription Factor RelA; D000109:Acetylcholine
keywords: bladder outlet obstruction; human bladder smooth muscle cell; hydrostatic pressure; inflammatory cytokine; muscarinic receptor