Shackelford R E, Alford P B, Xue Y, Thai S F, Adams D O, Pizzo S
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Mol Pharmacol. 1997 Sep;52(3):421-9. doi: 10.1124/mol.52.3.421.
Aspirin has been reported to inhibit the activation of nuclear factor-kappaB (NF-kappaB) through stabilization of inhibitor kappaB (IkappaB). This observation led us to investigate the role of aspirin in suppressing the activation of the NF-kappaB-regulated tumor necrosis factor-alpha (TNF-alpha) gene expression in primary macrophages. We now report that therapeutic doses of aspirin suppress lipopolysaccharide-inducible NF-kappaB binding to an NF-kappaB binding site in the TNF-alpha promoter, lipopolysaccharide-induced TNF-alpha mRNA accumulation, and protein secretion. IkappaB is also stabilized under these conditions. The aspirin-initiated stabilization of IkappaB, suppression of induced TNF-alpha mRNA, and NF-kappaB binding to the TNF-alpha promoter are blocked by pretreatment with pertussis toxin. These studies suggest that aspirin may exert significant anti-inflammatory effects by suppressing the production of macrophage-derived inflammatory mediators.
据报道，阿司匹林可通过稳定抑制蛋白κB（IkappaB）来抑制核因子-κB（NF-κB）的激活。这一观察结果促使我们研究阿司匹林在抑制原代巨噬细胞中NF-κB调节的肿瘤坏死因子-α（TNF-α）基因表达激活中的作用。我们现在报告，治疗剂量的阿司匹林可抑制脂多糖诱导的NF-κB与TNF-α启动子中NF-κB结合位点的结合、脂多糖诱导的TNF-α mRNA积累以及蛋白质分泌。在这些条件下，IkappaB也会稳定。阿司匹林引发的IkappaB稳定、诱导的TNF-α mRNA抑制以及NF-κB与TNF-α启动子的结合可被百日咳毒素预处理阻断。这些研究表明，阿司匹林可能通过抑制巨噬细胞衍生的炎症介质的产生发挥显著的抗炎作用。
