Suppression by dexamethasone of inducible nitric oxide synthase protein expression in vivo -: A possible role for lipocortin 1

被引:26
作者
Bryant, CE [1 ]
Perretti, M [1 ]
Flower, RJ [1 ]
机构
[1] Univ London St Bartholomews Hosp Med Coll, William Harvey Res Inst, Dept Biochem Pharmacol, London EC1M 6BQ, England
基金
英国惠康基金;
关键词
annexin; 1; glucocorticoid; macrophages; LPS; endotoxaemia;
D O I
10.1016/S0006-2952(97)00462-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Western blot and densitometric analysis of organ homogenates from lipopolysaccharide (LPS) treated rats (1-10 mg kg(-1), i.p.) exhibited a strong induction of inducible nitric oxide synthase (iNOS) expression seen at all the doses tested (1, 3, and 10 mg kg(-1), n = 3). In particular, 3 hr after challenge of rats with LPS, iNOS was detectable in the liver, kidney, aorta, spleen and lung. Dexamethasone (DEX) (0.1-1 mg kg(-1); -1 hr) dose dependently reduced iNOS expression in lung homogenates after exposure to LPS (1 mg kg(-1); P < 0.05). A partial reversal of DEX-induced suppression of iNOS expression in lung homogenates 3 hr after challenge with LPS was observed in rats which received a specific anti-lipocortin 1 sheep serum (LCS3; 1 mL kg(-1) 24 hr prior to the steroid), with an inhibition of 35 +/- 8%, as compared to animals passively immunised with normal sheep serum where dexamethasone exhibited an inhibition of 60 +/- 7% (n = 4). Peritoneal macrophages collected from rats treated with LPS (1 mg kg(-1); 3 hr) and cultured for 16 hr, released significant amounts of nitrite (51 +/- 1 mu M) into the cell supernatants; this was reduced (-70 +/- 6%) after pre-treatment with dexamethasone (0.3 mg kg(-1)) and this effect was neutralised if animals were passively immunised with LCS3 (P < 0.01; n = 4). Thus lipocortin 1 mediates, at least in part, the inhibitory action exerted by dexamethasone on both iNOS protein expression in lung and iNOS activity (as measured by nitrite release) in primary peritoneal cells of rats. (C) 1998 Elsevier Science Inc.
引用
收藏
页码:279 / 285
页数:7
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