Milano S, Arcoleo F, Dieli M, D'Agostino R, D'Agostino P, De Nucci G, Cillari E
Institute of General Pathology, University of Palermo, Italy.
Prostaglandins. 1995 Feb;49(2):105-15. doi: 10.1016/0090-6980(94)00004-g.
We have evaluated the role of prostaglandin E2 (PGE2) in the synthesis of nitric oxide (NO) by the activation of the inducible form of nitric oxide synthase (NOS) in the murine macrophage cell line, J774, stimulated with different doses of lipopolysaccharide (LPS). The stimulation of the J774 line with suboptimal doses of LPS (0.1 microgram/mL) caused a production of endogenous PGE2 that was capable of stimulating NOS activity inducing an increase in the NO synthesis, as attested by the fact that cyclooxygenase enzyme inhibitor, indomethacin, significantly reduced NO secretion. On the contrary, a higher dose of LPS (1 microgram/mL) produced high levels of PGE2 that reduced the levels of NOS and, subsequently, NO production. Experiments carried out with exogenous PGE2 indicated that concentrations between 1 and 10 ng/mL are able to stimulate the expression of NOS and the release of NO, while higher concentrations (> 50 ng/mL) are inhibitory. Furthermore, our data indicate that there is a network of interaction which involves NO, PGE2, and tumor necrosis factor. High levels of PGE2 inhibited TNF alpha secretion, which in turn could exert inhibitory effects on NO synthesis.
我们评估了前列腺素E2（PGE2）在小鼠巨噬细胞系J774中通过激活诱导型一氧化氮合酶（NOS）来合成一氧化氮（NO）的作用，该细胞系用不同剂量的脂多糖（LPS）刺激。用次优剂量的LPS（0.1微克/毫升）刺激J774细胞系会产生内源性PGE2，其能够刺激NOS活性，导致NO合成增加，这一点由环氧合酶抑制剂吲哚美辛显著降低NO分泌这一事实所证明。相反，较高剂量的LPS（1微克/毫升）产生高水平的PGE2，降低了NOS水平，随后减少了NO生成。用外源性PGE2进行的实验表明，1至10纳克/毫升的浓度能够刺激NOS的表达和NO的释放，而较高浓度（>50纳克/毫升）则具有抑制作用。此外，我们的数据表明存在一个涉及NO、PGE2和肿瘤坏死因子的相互作用网络。高水平的PGE2抑制肿瘤坏死因子α的分泌，这反过来又可能对NO合成产生抑制作用。
