Abstract
A major component in green tea, epigallocatechin-3-gallate (EGCG), is reported to interfere with different steps of a number of inflammatory pathways. After oral administration, EGCG is retained in the gastrointestinal tract, where it is thought to exert preventive functions against inflammatory bowel disease and colon cancer. In this study, the human colon adenocarcinoma cell lines HT29 and T84 were used to investigate the effect of EGCG on intestinal inflammation. HT29 and T84 cells were stimulated with tumor necrosis factor (TNF)-α to induce the inflammatory condition and to trigger the inflammatory cascade in vitro and treated with EGCG to study its effect on inflammatory processes. The secretion of the chemokines interleukin (IL)-8, macrophage inflammatory protein (MIP)-3α, and prostaglandin E2 (PGE2) was determined by enzyme-linked immunosorbent assay. The gene expression level was measured by quantitative real-time polymerase chain reaction. Treatment of TNF-α-stimulated HT29 cells with EGCG dose-dependently inhibited the synthesis of IL-8, MIP-3α, and PGE2. Treatment with EGCG also inhibited the production of IL-8 and MIP-3α in TNF-α-stimulated T84 cells. Gene expression analysis in both HT29 and T84 cells revealed that EGCG down-regulates genes involved in inflammatory pathways. This study shows that EGCG acts broadly on the production of chemokines and PGE2 in the chemokine and eicosanoid pathways of colon epithelial cells. Therefore, EGCG might prove useful for the prevention and/or attenuation of colonic disorders.
Footnotes
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doi:10.1124/jpet.105.090167.
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ABBREVIATIONS: PML, polymorphonuclear leukocyte; IL, interleukin; MIP, macrophage inflammatory protein; GRO, growth-regulated oncogene; PGE2, prostaglandin E2; COX, cyclooxygenase; EGCG, epigallocatechin-3-gallate; TNF, tumor necrosis factor NF-κB, nuclear factor κB; DMEM, Dulbecco's modified Eagle's medium; FBS, fetal bovine serum; LDH, lactate dehydrogenase; ELISA, enzyme-linked immunosorbent assay; PBS, phosphate-buffered saline; PBS-T, PBS containing 0.05% Tween 20; RT, real time; PCR, polymerase chain reaction; RANK, receptor activator of NF-κB; ΔCT, (threshold cycle reference genes) – (threshold cycle unknown gene); LOX, lipoxygenase; RANTES, regulated on activation normal T cell expressed and secreted; IBD, inflammatory bowel disease.
- Received May 30, 2005.
- Accepted August 16, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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