title: Effects of epigallocatechin gallate on regulatory T cell number and function in obese v. lean volunteers.
abstract: Obesity predisposes to an increased incidence of diabetes and CVD. Also, obesity is a pro-inflammatory state. Regulatory T cells (Tregs) are essential negative regulators of inflammation and are down-regulated in pro-inflammatory states. Animal models of obesity are associated with decreased Tregs. The dietary modulation of Tregs could be used as a therapeutic strategy to control inflammation. Epigallocatechin gallate (EGCG) is a potent anti-inflammatory agent and an active ingredient of green tea and is suggested to have a role as a preventive agent in obesity, diabetes and CVD. The role of EGCG in the modulation of Tregs has, however, not been studied. Thus, the aim of the present study was to determine the effect of EGCG on the number and function of Tregs in obese and lean human subjects in vitro, and to delineate its specific regulation mechanisms. Tregs were isolated from normal-weight and obese subjects. Tregs were cultured in the absence or presence of EGCG (20 mum) for 24 h. Foxp3-expressing Tregs were enumerated using flow cytometry. Histone deacetylase (HDAC) activity and nuclear NF-kappaBp65 level were measured by ELISA and Western blots. Obese subjects had lower Tregs and IL-10 production than lean subjects. EGCG treatment significantly enhanced the number of Foxp3-expressing Tregs and IL-10 production in vitro (P < 0.05) in both groups. Also, EGCG decreased NF-kappaB activity and increased HDAC activity and HDAC-2 expression in Tregs (P < 0.05) in both groups. Thus, in part, EGCG enhances the functionality of Tregs, i.e. IL-10 production and number by suppressing the NF-kappaB signalling pathway via inducing epigenetic changes.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Davis, Medical Center, Sacramento, CA, USA.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Yun
authors.forename: Ishwarlal
authors.initials: I
authors.lastname: Jialal
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D028241:Camellia sinensis / Q000737:chemistry*; D016022:Case-Control Studies; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018929:Cell Culture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D044127:Epigenesis, Genetic; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000276:immunology; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism; D013851:Thinness / Q000276:immunology; D051996:Transcription Factor RelA / Q000378:metabolism; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D010936:Plant Extracts; D051996:Transcription Factor RelA; D016753:Interleukin-10; D002392:Catechin; C045651:epigallocatechin gallate; D006655:Histone Deacetylases