Immune cell activation and subsequent epithelial dysfunction by Staphylococcus enterotoxin B is attenuated by the green tea polyphenol (-)-epigallocatechin gallate.
Bacterial superantigens (SAg) are potent T cell activators and when delivered systemically elicit a self-limiting enteropathy in mice. Also, SAg-stimulated human peripheral blood mononuclear cells (PBMC) increase enteric epithelial cell monolayer permeability in vitro. Epigallocatechin gallate (EGCG), the major polyphenol component of green tea (Camilla sinesis) leaf, has been presented as an anti-inflammatory agent. We tested the hypothesis that EGCG (10-100 microM) would block PBMC activation by the SAg, Staphylococcus aureus enterotoxin B (SEB, 1 microg/ml), thus preventing disruption of the epithelial barrier. Pretreatment or co-treatment of human PBMC or murine lymphnode cells with EGCG significantly reduced SEB-induced proliferation and IL-2, IFNgamma, and TNFalpha production. ConA-induced proliferation was also inhibited by EGCG (50 microM) co-treatment. These effects of EGCG were not due to induction of immune cell apoptosis, and were independent of EGCGs anti-oxidant activity, and inhibition of NF-kappaB or AP-1 activation. Moreover, addition of exogenous IL-2 (20 ng/ml) to the cultures could not overcome the immunosuppressive effect of EGCG. Culture supernatant from PBMC stimulated in the presence of EGCG failed to increase the permeability of T84 epithelial cell monolayers: a finding consistent with the reduced IFNgamma and TNFalpha production by SAg+EGCG treated PBMC. These data promote EGCG as a suppressor of T cell activation, and given the prominent role that bacteria and T cells play in inflammatory disease we suggest that EGCG could be a useful addition to current treatments for enteric immune disorders and T cell driven immunopathologies.
Watson
James L
JL
Intestinal Disease Research Programme, Department of Pathology and Molecular Medicine, McMaster University, Ont., Canada.
Vicario
Maria
M
Wang
Arthur
A
Moreto
Miquel
M
McKay
Derek M
DM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D028241:Camellia sinensis; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D024202:Electrophoretic Mobility Shift Assay; D004768:Enterotoxins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000276:immunology / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004768:Enterotoxins; D007376:Interleukin-2; D016328:NF-kappa B; D010936:Plant Extracts; D018808:Transcription Factor AP-1; C465546:green tea extract AR25; C031818:enterotoxin B, staphylococcal; D002392:Catechin; C045651:epigallocatechin gallate