Virginia College of Osteopathic Medicine, Blacksburg, VA 24060, USA.
Cell Mol Immunol. 2010 Mar;7(2):123-32. doi: 10.1038/cmi.2010.1. Epub 2010 Feb 8.
Epigallocatechin-3-gallate (EGCG), a bioactive component of green tea, has been reported to exert anti-inflammatory effects on immune cells. EGCG is also shown to activate the metabolic regulator, adenosine 5'-monophosphate-activated protein kinase (AMPK). Reports have also indicated that EGCG inhibits the immune-stimulated phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. The PI3K/Akt/mTOR pathway has been implicated in mesangial cell activation in lupus. Mesangial cells from MRL/lpr lupus-like mice are hyper-responsive to immune stimulation and overproduce nitric oxide (NO) and other inflammatory mediators when stimulated. In our current studies, we sought to determine the mechanism by which EGCG attenuates immune-induced expression of pro-inflammatory mediators. Cultured mesangial cells from MRL/lpr mice were pre-treated with various concentrations of EGCG and stimulated with lipopolysaccharide (LPS)/interferon (IFN)-gamma. EGCG activated AMPK and blocked LPS/IFN-gamma-induced inflammatory mediator production (iNOS expression, supernatant NO and interleukin-6). Interestingly, EGCG attenuated inflammation during AMPK inhibition indicating that the anti-inflammatory effect of EGCG may be partially independent of AMPK activation. Furthermore, we found that EGCG effectively inhibited the immune-stimulated PI3K/Akt/mTOR pathway independently of AMPK, by decreasing phosphorylation of Akt, suggesting an alternate mechanism for EGCG-mediated anti-inflammatory action in mesangial cells. Taken together, these studies show that EGCG attenuated inflammation in MRL/lpr mouse mesangial cells via the PI3K/Akt/mTOR pathway. Our findings suggest a potential therapeutic role for the use of EGCG to regulate inflammation and control autoimmune disease.
没食子酸表没食子儿茶素酯（EGCG）是绿茶中的一种生物活性成分，据报道它对免疫细胞具有抗炎作用。EGCG 还能激活代谢调节剂，即 5'-单磷酸腺苷激活蛋白激酶（AMPK）。有报道称，EGCG 可抑制免疫刺激的磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）通路。PI3K/Akt/mTOR 通路与狼疮中系膜细胞的激活有关。MRL/lpr 狼疮样小鼠的系膜细胞对免疫刺激非常敏感，受到刺激时会过度产生一氧化氮（NO）和其他炎症介质。在我们目前的研究中，我们试图确定 EGCG 减轻免疫诱导的促炎介质表达的机制。用不同浓度的 EGCG 预处理来自 MRL/lpr 狼疮样小鼠的培养系膜细胞，并用脂多糖（LPS）/干扰素（IFN）-γ刺激。EGCG 激活了 AMPK 并阻断了 LPS/IFN-γ诱导的炎症介质产生（iNOS 表达、上清液 NO 和白细胞介素-6）。有趣的是，EGCG 在 AMPK 抑制期间减轻了炎症，表明 EGCG 的抗炎作用可能部分独立于 AMPK 激活。此外，我们发现 EGCG 通过降低 Akt 的磷酸化，有效地抑制了免疫刺激的 PI3K/Akt/mTOR 通路，而不依赖于 AMPK，这表明 EGCG 在系膜细胞中发挥抗炎作用的另一种机制。总之，这些研究表明，EGCG 通过 PI3K/Akt/mTOR 通路减轻了 MRL/lpr 小鼠系膜细胞的炎症。我们的研究结果表明，使用 EGCG 来调节炎症和控制自身免疫性疾病可能具有潜在的治疗作用。
