title: The effect of endothelin-1 on the production of interleukin-6 in cultured human detrusor smooth muscle cells, and the effect of interleukin-6 on the contractile response of bladder smooth muscle strips from rats.
abstract: OBJECTIVE
  To determine the effect of endothelin-1 (ET-1) on the production of interleukin-6 (IL-6) in cultured human detrusor smooth muscle cells (HDSMCs) and the effect of IL-6 on the contractile response of bladder smooth muscle strips from rats.
  
  
  METHODS
  The expression of IL-6 mRNA and production of IL-6 protein in cultured HDSMCs treated with the different concentrations of ET-1 were assayed by reverse transcriptase-polymerase chain reaction and specific enzyme-linked immunosorbent assay, respectively. The strips from Sprague-Dawley rats were either untreated or treated with 1 ng/mL of IL-6 for 60 min. Using increasing cumulative concentrations of acetylcholine (ACh), bethanechol (BCh), or sodium nitroprusside, we assessed the concentration-contraction or the relaxation responses. In cystitis-induced strips, change of contractions induced by noradrenaline (NA) with or without treatment of IL-6 were assessed. The IL-6-treated strips were incubated for 30 min in the presence or absence indomethacin or SQ29548, and then the effects on ACh- or BCh-induced contractions were measured.
  
  
  RESULTS
  The expression of IL-6 mRNA and the production of IL-6 protein on the cultured HDSMCs pretreated by ET-1 were significantly higher than in the control (P<0.05). The ACh- and BCh-induced contractions were increased in the IL-6 pretreated strips from both dome and trigone, regardless of the presence of urothelium (P<0.05). The presence of cystitis augmented the NA-induced contractions (P<0.05). The contractions induced by ACh and BCh were inhibited by indomethacin and SQ29548.
  
  
  CONCLUSIONS
  ET-1 induces expression of IL-6 mRNA and production of IL-6 protein on HDSMCs. IL-6 enhances detrusor smooth muscle contractility via the muscarinic or adrenergic receptor pathway.
authors.affiliation: Department of Urology, KEPCO Medical Foundation Hanil General Hospital, and Department of Physiology, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: June Hyun
authors.initials: JH
authors.lastname: Han
authors.forename: Moo Yeol
authors.initials: MY
authors.lastname: Lee
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Myung
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003556:Cystitis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005231:Fatty Acids, Unsaturated; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001743:Urinary Bladder / Q000502:physiology*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D015850:Interleukin-6; D012333:RNA, Messenger; C045749:SQ 29548; D007213:Indomethacin