Epigallocatechin-3-Gallate Inhibits Secretion of TNF-α, IL-6 and IL-8 through the Attenuation of ERK and NF-κB in HMC-1 Cells

Abstract

Background: Epigallocatechin-3-gallate (EGCG) is a major form of tea catechin and has a variety of biological activities. In the present study, we investigated the effect of EGCG on the secretion of TNF-α, IL-6 and IL-8, as well as its possible mechanism of action by using the human mast cell line (HMC-1). Methods: EGCG was treated before the activation of HMC-1 cells with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore (A23187). To investigate the effect of EGCG on PMA+A23187-stimulated HMC-1 cells, ELISA, Western blot analysis, electrophorectic mobility shift assay and luciferase assay were used in this study. Results: EGCG (100 µM) inhibited PMA+A23187-induced TNF-α, IL-6 and IL-8 expression and production. EGCG inhibited the intracellular Ca²⁺ level. EGCG attenuated PMA+A23187-induced NF-ĸB and extracellular signal-regulated kinase (ERK1/2) activation, but not that of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. Conclusion: EGCG inhibited the production of TNF-α, IL-6 and IL-8 through the inhibition of the intracellular Ca²⁺ level, and of ERK1/2 and NF-ĸB activation. These results indicate that EGCG may be helpful in regulating mast-cell-mediated allergic inflammatory response.

TLR4 Signaling Inhibitory Pathway Induced by Green Tea Polyphenol Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor

“…It has been described that EGCG suppresses LPS-induced activation of NF-kB by blocking the degradation of IkB-a following IkB-a phosphorylation (7). In addition, EGCG was found to inhibit the production of inflammation mediators, such as TNF-a, IL-6, and IL-8, through the inhibition of the intracellular Ca 2+ level (43). Furthermore, 50 mM EGCG was reported to be able to modulate both MyD88-and TRIF-dependent signaling pathways of TLRs (16).…”

Epigallocatechin-3-Gallate Ameliorates Experimental Autoimmune Encephalomyelitis by Altering Balance among CD4+ T-Cell Subsets

“…First, reduced pathological cells in the periphery are assumed to reduce the frequency of these cells coming across the CNS. Second, EGCG reduces the production or expression of the molecules known to facilitate leukocyte transendothelial migration, such as chemokines IL-8 and monocyte chemoattractant protein-1 [45][46][47] and adhesion molecules 48,49 and to inhibit migration of neutrophils, 50,51 CD8 ϩ T cells, 49 and B cells. 52 Third, the observed EGCG-induced reduction in IFN-␥ and IL-17 production and the proportion of IL-17-IFN-␥ double-positive CD4 ϩ T cells may contribute to the reduced leukocyte infiltration because, as reported, IFN-␥ facilitates Th17 migration across the BBB by enhancing endothelial expression of adhesion molecule ICAM-1, and IL-17 is capable of disrupting the BBB; IL-17-IFN-␥ double-positive cells have a higher capacity for crossing the BBB than either singlepositive cells.…”

Butrin, Isobutrin, and Butein from Medicinal PlantButea monospermaSelectively Inhibit Nuclear Factor-κB in Activated Human Mast Cells: Suppression of Tumor Necrosis Factor-α, Interleukin (IL)-6, and IL-8

“…Because these cells contain a variety of potent mediators, including histamine, heparin, proteinases, leukotrienes, and multifunctional cytokines (Woolley and Tetlow, 2000), its potential contributions to the processes of inflammation and matrix degradation have recently become evident (Maruotti et al, 2007). The human mast cell line HMC-1 is a useful tool for studying cytokine activation pathways (Shin et al, 2007). The spectrum of proteins and other molecules produced by HMC-1 cells with PMACI stimulation supports the well recognized role of mast cells in inflammation (Azzolina et al, 2003;Shin et al, 2007).…”