Department of Immunology, School of Medicine, Keimyung University, Jung-Gu, Taegu, South Korea.
Int Immunopharmacol. 2009 May;9(5):614-9. doi: 10.1016/j.intimp.2009.02.002. Epub 2009 Feb 21.
We here investigated the functional effect of withaferin A on airway inflammation and its action mechanism. Withaferin A inhibited the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human lung epithelial A549 cells stimulated with tumor necrosis factor-alpha (TNF-alpha), resulting in the suppression of leukocyte adhesion to lung epithelial A549 cells. In addition, withaferin A inhibited TNF-alpha-induced expression of adhesion molecules (ICAM-1 and VCAM-1) protein and mRNA in a dose-dependent manner. Withaferin A prevented DNA binding activity of nuclear factor-kappaB (NF-kappaB) and nuclear translocation of NF-kappaB. It also inhibited phosphorylation of Akt and extracellular signal-regulated kinase (ERK), which are upstream in the regulation of adhesion molecules by TNF-alpha. Furthermore, withaferin A inhibited U937 monocyte adhesion to A549 cells stimulated by TNF-alpha, suggesting that it may inhibit the binding of these cells by regulating the expression of critical adhesion molecules by TNF-alpha. Taken together, these results suggest that withaferin A inhibits cell adhesion through inhibition of ICAM-1 and VCAM-1 expression, at least in part, by blocking Akt and down-regulating NF-kappaB activity.
我们在此研究了醉茄素 A 对气道炎症的功能影响及其作用机制。醉茄素 A 抑制了肿瘤坏死因子-α (TNF-α) 刺激的人肺上皮 A549 细胞中细胞间黏附分子-1 (ICAM-1) 和血管细胞黏附分子-1 (VCAM-1) 的表达，从而抑制白细胞与肺上皮 A549 细胞的黏附。此外，醉茄素 A 呈剂量依赖性抑制 TNF-α诱导的黏附分子（ICAM-1 和 VCAM-1）蛋白和 mRNA 的表达。醉茄素 A 可阻止核因子-κB（NF-κB）的 DNA 结合活性和 NF-κB 的核转位。它还抑制 Akt 和细胞外信号调节激酶 (ERK) 的磷酸化，而 Akt 和 ERK 是 TNF-α调节黏附分子的上游分子。此外，醉茄素 A 抑制 TNF-α刺激的 U937 单核细胞与 A549 细胞的黏附，提示它可能通过调节 TNF-α 诱导的关键黏附分子的表达来抑制这些细胞的黏附。综上所述，这些结果表明醉茄素 A 通过抑制 Akt 并下调 NF-κB 活性，至少部分抑制了 ICAM-1 和 VCAM-1 的表达，从而抑制细胞黏附。
