Effect of the green tea catechin, epigallocatechin gallate, on innate immune responses in HIV-1 infection as a microbicide (P3170)

Abstract

Abstract Our preclinical data showed binding of green tea catechin, epigallocatechin gallate(EGCG), to CD4 with inhibition of HIV-1-gp120 binding to human CD4+Tcells throughout a broad spectrum of virus strains lead to implementation of our Phase I/IIa clinical trial in HIV-1-infected indivduals. As mucosal dendritic cells(DC), Langerhans cells(LC) and monoctye-derived dendritic cells(MDDC), with CD4 receptor binding to HIV-1-gp120, act as first line defense in mucosa against invading pathogens via innate immune responses,EGCG in the context of an HIV-1 microbicide was studied. Human CD34+ hematopoietic stem cells and CD14+ cells differentiatied to LC and MDDC,respectively were assessed for HIV-1-gp120 binding, Annexin V-binding apopotosis and receptor profiling by flow cytometry, cytokine profiling by Luminex, toll-like receptor(TLR) profiling by RT-PCR, antigen uptake/presentation(APC) by RIA, cytotoxicity by MTT and statistical significance by Student’s t test. EGCG(1-50uM) downregulated TLR-6,-8 mRNA expresion (25%;p<0.05;43%;p<0.01, respectively),not TLR-2 or-3. TLR9 ligation downregulated CD86 expression and was reversed by EGCG (50uM) (62%;p<0.05).EGCG (1-50uM) did not significantly increase DC cytotoxicity, apoptosis, APC nor promote proinflammatory ctyokine secretiion of TNFa,IL1a,IL1B,orIL6. R5 chemokines, MIP1a,MIP1BandRANTES were upregulated by EGCG (25uM) (29%,33%,37%,respectively;p<0.01). EGCG has potential as an HIV-1 microbicide.