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. MATERIALS AND 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.