Green Tea Extract Blocks the TRIF‐Mediated TLR4 Signaling Cascade

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Green tea has long been known for its efficacy in immune diseases however only recently have we examined the mechanisms of its effects. Studies have shown that green tea has a profound effect on LPS induced TLR4 signaling in peritoneal macrophages in mice. The present study investigated the levels of several chemokines upregulated through the TRIF adaptor protein during TLR4 activation. Peritoneal macrophages from C57BL/6 mice were treated with various concentrations of green tea extract (GTE; 1μg/ml, 10μg/ml, 100μg/ml) and LPS (100ng/ml) for 24 hours. Expression of B7.1/CD80, B7.2/CD86 and MHCII were detected by flow cytometry. Expression of IP10, IL1β, TNFα and CCL5 (RANTES) were quantified by ELISA. The data demonstrates that GTE downregulates TRIF dependent chemokines after LPS-induced TLR4 activation. Indeed, GTE reduced chemokine and co-stimulatory molecule expression from murine peritoneal macrophages to control levels. IP10 was increased to 1.5 pg/ml by LPS and GTE reduced the levels back to control (undetectable), in a dose dependent manner. Similarly, IL1β expression (control - undetectable, LPS - 8.7 pg/ml, LPS + GTE – undetectable) and CCL5 expression (control – 104.5, LPS - 550 pg/ml, LPS+ GTE – 47.7 pg/ml) were significantly reduced. Further, flow cytometry demonstrated that GTE inhibited LPS induced expression of B7 molecules and MHCII. The clinical relevance of this study is its potential impact in reducing allograft rejection. The release of CCL5 by T cells and both IL1β and TNFα from peritoneal macrophages is the signature of late graft rejection. If GTE can supplement, reduce or eliminate the need for immunosuppressants in transplantation, fewer transplant patients will suffer late rejection.