The Inhibitory Effect Of EGCG On FMLF-induced Leukocytes Activation

Phagocytic leukocytes infiltrate the sites of inflammation, injury and bacterial infection presumably in response to locally produced chemotactic factors. Over the past thirty years, a number of exogenous and host-derived chemoattractants have been identified. The "classical" chemoattractants include bacterial peptideN-formyl-methionyl-leucyl-phenyl-alamine (fMLF), activated complement components (C3a and C5a), leukotriene B4 (LTB4) and platelet-activating factor (PAF). There is also a superfamily of chemokines that induce the migration of selected cell population. Both classical chemoattractant and chemokine family members use seven-transmembrane, G protein-coupled receptors to chemoattract and activate leukocytes. Recently, accumulating evidence suggests that in addition to mediating leukocyte chemotaxis, chemoattractants play essential roles in hematopoiesis, development, immune response, HIV infection, and progression of malignant tumors. Thus, identification of molecules capable of interaction with chemoattractants or their receptors will be benefit for developing therapeutic agents against chemoattractant and receptor-related diseases.Epigallocatechin gallate (EGCG) is the major polyphenol component of green tea and has been known to have a variety of activities such as antioxidant, anticarcinogenic, anti-inflammatory, cardiovascular protective and neuroprotective activities. EGCG was reported to inhibit leukocyte migration in response to chemokines such as IL-8, CINC and MIP-2, to trap reactive oxygen species, to inhibit neutrophil degranulation and inhibit inflammatory mediator release.In this study we examined the effect of EGCG on chemotactic activity of several chemoattractants. Pretreatment of human monocytic leukemia cell line THP-1 with 300 μM EGCG significantly inhibited chemotactic response to 10-50 ng/ml SDF-1α and 0.1-1.0 nM fMLF, but enhanced cell response to 1-10 ng/ml MCP-1 and 1-10 μM MMK-1. Further studies with THP-1 cell and fMLF receptor FPR expressing cell ETFR showed that EGCE inhibited cell migration and calcium mobilization in response to fMLF in a...