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.
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.
Han
June Hyun
JH
Department of Urology, KEPCO Medical Foundation Hanil General Hospital, and Department of Physiology, College of Medicine, Chung-Ang University, Seoul, Korea.
Lee
Moo Yeol
MY
Myung
Soon Chul
SC
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*
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