Open AccessEpigallocatechin-3-gallate (EGCG) attenuates inflammation in MRL/lpr mouse mesangial cells
Author(s) -
Abigail Peairs,
Rujuan Dai,
Lu Gan,
Samuel K. Shimp,
Marissa Nichole Rylander,
Liwu Li,
Christopher M. Reilly
Publication year - 2010
Publication title -
cellular and molecular immunology/cellular and molecular immunology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 2.5
H-Index - 81
eISSN - 2042-0226
pISSN - 1672-7681
DOI - 10.1038/cmi.2010.1
Subject(s) - pi3k/akt/mtor pathway , ampk , protein kinase b , inflammation , immune system , chemistry , protein kinase a , mtorc1 , signal transduction , phosphorylation , cancer research , microbiology and biotechnology , biology , immunology , biochemistry
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.