摘要
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 MRUIpr 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/Ipr mice were pre-treated with various concentrations of EGCG and stimulated with lipopolysaccharide （LPS）/interferon （IFN）-γ. EGCG activated AMPK and blocked LPS/ IFN-γ-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/Ipr 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.
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 MRUIpr 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/Ipr mice were pre-treated with various concentrations of EGCG and stimulated with lipopolysaccharide （LPS）/interferon （IFN）-γ. EGCG activated AMPK and blocked LPS/ IFN-γ-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/Ipr 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.
