Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea.
Int Immunopharmacol. 2011 Aug;11(8):1137-42. doi: 10.1016/j.intimp.2011.02.029. Epub 2011 Mar 21.
Microglia are the major immune effector cells in the brain, and microglia activated by injury and infection can produce inflammatory mediators. A number of studies have reported that withaferin A has anti-inflammatory functions. However, the effects of withaferin A on the microglial inflammatory response have not been investigated. Our results show that withaferin A inhibited lipopolysaccharide (LPS)-induced cyclooxygenase (COX)-2 mRNA and protein expression and prostaglandin E2 (PGE(2)) production in BV2 murine microglial cells. Withaferin A had no effect on LPS-induced Akt and ERK phosphorylation, but phosphorylation of p38 and JNK was slightly decreased by withaferin A. Withaferin A significantly inhibited LPS-induced STAT1 and STAT3 phosphorylation in a dose-dependent manner. Furthermore, withaferin A inhibited nuclear translocation of STAT1 and interferon-gamma activated sequence (GAS)-promoter activity. Taken together, these results suggest that withaferin A inhibits LPS-induced PGE(2) production and COX-2 expression, at least in part, by blocking STAT1 and STAT3 activation.
小胶质细胞是大脑中的主要免疫效应细胞，受伤和感染激活的小胶质细胞可产生炎症介质。许多研究报告称，醉茄素 A 具有抗炎功能。然而，醉茄素 A 对小胶质细胞炎症反应的影响尚未得到研究。我们的结果表明，醉茄素 A 抑制脂多糖（LPS）诱导的环氧化酶（COX）-2 mRNA 和蛋白表达以及前列腺素 E2（PGE2）的产生在 BV2 鼠小胶质细胞中。醉茄素 A 对 LPS 诱导的 Akt 和 ERK 磷酸化没有影响，但醉茄素 A 使 p38 和 JNK 的磷酸化略有减少。醉茄素 A 显著抑制 LPS 诱导的 STAT1 和 STAT3 磷酸化呈剂量依赖性。此外，醉茄素 A 抑制了 STAT1 的核易位和干扰素-γ激活序列（GAS）-启动子活性。综上所述，这些结果表明醉茄素 A 通过阻断 STAT1 和 STAT3 的激活，抑制 LPS 诱导的 PGE2 产生和 COX-2 表达。
