Novel actions of aspirin and sodium salicylate: Discordant effects on nitric oxide synthesis and induction of nitric oxide synthase mRNA in a murine macrophage cell line
Novel actions of aspirin and sodium salicylate: Discordant effects on nitric oxide synthesis and induction of nitric oxide synthase mRNA in a murine macrophage cell line
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DOI：
10.1002/jlb.59.6.840
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发表时间：
1996-06-01
影响因子：
5.5
通讯作者：
Morris, SM
中科院分区：
文献类型：
--
作者：
KepkaLenhart, D;Chen, LC;Morris, SM
在受到脂多糖 (LPS) 或干扰素-γ (IFN-γ) 刺激后，阿司匹林和水杨酸钠均以相似程度抑制 RAW 264.7 鼠巨噬细胞系中一氧化氮 (NO) 的产生。阿司匹林和水杨酸钠的相似效力表明细胞大分子的乙酰化对于观察到的效果并不是必需的。添加的前列腺素E(2)未能克服阿司匹林或水杨酸钠的作用，这表明这些作用不仅仅是抑制前列腺素合成的结果。无论这些药物对 LPS 或 IFN-γ 诱导一氧化氮合酶 (iNOS) mRNA 的影响如何，都会抑制 NO 产生。阿司匹林和水杨酸钠抑制 LPS 刺激的细胞中 iNOS mRNA 的诱导，但增强 IFN-γ 刺激的细胞中 iNOS mRNA 的诱导。相反，这些药物始终抑制 LPS 和 IFN-γ 刺激的细胞中精氨酸琥珀酸合成酶 mRNA 的诱导。 3-10 mM 范围内的阿司匹林浓度抑制诱导的 NO 产生和 iNOS 蛋白的表达，而不抑制 iNOS mRNA 的诱导。对 NO 合成的影响与 iNOS mRNA 诱导之间的不一致表明，阿司匹林和水杨酸钠对参与刺激的 RAW 264.1 细胞产生 NO 的途径有多个作用位点。
Aspirin and sodium salicylate each inhibit to a similar extent the production of nitric oxide (NO) in the RAW 264.7 murine macrophage cell line following stimulation by either lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma). The similar potencies of aspirin and sodium salicylate indicate that acetylation of cellular macromolecules is not essential for the observed effects. The failure of added prostaglandin E(2) to overcome the effects of aspirin or sodium salicylate indicates that these effects are not simply the result of inhibition of prostaglandin synthesis. The inhibition of NO production occurs irrespective of the effect of these agents on induction of nitric oxide synthase (iNOS) mRNA by LPS or IFN-gamma. Aspirin and sodium salicylate inhibit iNOS mRNA induction in LPS-stimulated cells but enhance iNOS mRNA induction in IFN-gamma-stimulated cells. In contract, these agents consistently inhibit induction of argininosuccinate synthetase mRNA in both LPS- and IFN-gamma-stimulated cells. Concentrations of aspirin in the 3-10 mM range inhibit induced NO production and expression of iNOS protein without inhibiting induction of iNOS mRNA. Discordances between effects on NO synthesis and induction of iNOS mRNA indicate that aspirin and sodium salicylate have multiple sites of action in their effects on pathways that are involved in the production of NO by stimulated RAW 264.1 cells.