Epigallocatechin-3-gallate exhibits immunomodulatory effects in human primary T cells

T cells secrete several inflammatory cytokines that play a critical role in the progression of atherosclerosis. Although green tea epigallocatechin-3-gallate (EGCG) exerts anti-inflammatory and anti-atherosclerotic effects in animals, few studies have identified the mechanism underlying these effects in human primary T cells. This study investigated the pathway involved in EGCG modulation of cytokine secretion in activated human primary T cells. We pre-treated human primary T cells with EGCG (0.1, 1, 5, 10, and 20 mu M) for 4 h and incubated them with or without phorbol 12-myristate 13-acetate and ion-omycin (P/I) for 20 h. The cytokine production, activator protein (AP)-1 binding activity, and level of mitogen-activated protein kinase (MAPK) were assessed using enzyme-linked immunosorbent assay, electrophoretic mobility shift assay, and Western blotting, respectively. At 10 and 20 mM, EGCG decreased interleukin (IL)-2 levels by 26.0% and 38.8%, IL-4 levels by 41.5% and 55.9%, INF-gamma levels by 31.3% and 34.7%, and tumor-necrosis factor (TNF)-alpha levels by 23.0% and 37.6%, respectively. In addition, the level of phosphorylated c-Jun N-terminal (p-JNK) and extracellular signal-regulated kinase (p-ERK) was decreased, but not the level of p-p38 MAPK. EGCG did not alter any of the total protein amounts, suggesting a selective effect on specific types of MAPKs in stimulated human T cells. EGCG tended to inactivate AP-1 DNA-binding activity. The P/I-induced production of IL-2, IL-4, INF-gamma, and TNF-alpha by human T cells was suppressed by AP-1 inhibitor in a concentration-dependent manner. In conclusion, EGCG suppressed cytokine secretion in activated human primary T cells, and this effect was likely mediated by AP-1 inactivation through the ERK and JNK, but not p38 MAPK, pathways. These results may be related to the mechanisms through which EGCG inhibits immune- or inflammation-related atherogenesis. (C) 2021 The Authors. Published by Elsevier Inc.