Di Rosa M, Radomski M, Carnuccio R, Moncada S
Wellcome Research Laboratories, Beckenham, Kent, U.K.
Biochem Biophys Res Commun. 1990 Nov 15;172(3):1246-52. doi: 10.1016/0006-291x(90)91583-e.
The effect of glucocorticoids on the production of NO2- and NO by the macrophage cell line J774 was investigated. Stimulation of the cells with lipopolysaccharide (LPS) resulted in a time-dependent accumulation of NO2- in the medium, reaching a plateau after 48h. Concomitant incubation of the cells for 24h with dexamethasone (0.001-1.0 microM) or hydrocortisone (0.01-10.0 microM) caused a concentration-dependent inhibition of NO2- formation. The cytosol of J774 cells stimulated with LPS and IFN-gamma produced a time-dependent increase in the release of NO. This was blocked in a concentration-dependent manner by dexamethasone and hydrocortisone, but not progesterone, administered concomitantly with the immunological stimulus. None of these compounds had any effect on the release of NO once the enzyme had been induced. The inhibitory effect of hydrocortisone on NO formation was blocked by cortexolone. These data suggest that part of the anti-inflammatory and immunosuppressive actions of glucocorticoids is due to their inhibition of the induction of the NO synthase.
研究了糖皮质激素对巨噬细胞系J774产生NO2-和NO的影响。用脂多糖（LPS）刺激细胞导致培养基中NO2-随时间积累，48小时后达到平台期。将细胞与地塞米松（0.001 - 1.0微摩尔）或氢化可的松（0.01 - 10.0微摩尔）共同孵育24小时，会导致NO2-形成呈浓度依赖性抑制。用LPS和IFN-γ刺激的J774细胞的胞质溶胶中，NO的释放随时间增加。与免疫刺激同时给予的地塞米松和氢化可的松以浓度依赖性方式阻断了这种增加，但孕酮没有。一旦酶被诱导，这些化合物对NO的释放均无任何影响。氢化可的松对NO形成的抑制作用被皮质酮阻断。这些数据表明，糖皮质激素的部分抗炎和免疫抑制作用是由于它们对一氧化氮合酶诱导的抑制。
