Effects of ? opioid receptor agonist U50488H on angiotensinⅡ-induced production of interleukin-6 and interleukin-8 from endothelial cells / 中国药理学通报

ABSTRACT

Aim To examine the effect of ? opioid receptor agonist U50488H on the levels of interleukin-6(IL-6) and interleukin-8(IL-8) from angiotensinⅡ(AngⅡ) stimulated endothelial cells.Methods In the in vivo study,the modulation of U50488H(1.5 mg?kg~-1) intravenously on the level of AngⅡ was evaluated.In the in vitro study,endothelial cells from human umbilical vein(HUVEC) were cultured and divided into four groupsControl group,AngⅡ group,and AngⅡ plus U50488H and/or nor-BNI(a selective ? opioid receptor antagonist) group.These groups were treated respectively with phosphate buffered solution(PBS),AngⅡ(10~-9~10~-5 mol?L~-1),and AngⅡ in the presence of U50488H and/or nor-BNI for 0~24 hours.Culture supernatant and endothelial cells were collected at 0,3,6,12 and 24 h.IL-6 and IL8 levels in culture supernatant were measured by enzyme linked immunosorbent assay(ELISA).Results The level of AngⅡ in the blood was significantly decreased following U50488H intravenously,which was blocked by nor-BNI administration(2 mg?kg~-1).AngⅡ stimulated the productions of IL-6 and IL-8 from HUVEC in the dose-dependent and time-dependent manners.U50488H at 10~-5 mol?L~-1 significantly inhibited this process,and the inhibitory effect of U50488H was blocked by nor-BNI,which itself had no effect.Conclusion ? opioid receptor may play a role in the process of anti-inflammation via down regulation of AngⅡ level and inhibition of the AngⅡ-stimulated IL-6 and IL-8 productions from endothelium cells.