title: Natural indoles, indole-3-carbinol and 3,3'-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression.
abstract: Staphylococcal enterotoxin B (SEB) is a potent exotoxin produced by the Staphylococcus aureus. This toxin is classified as a superantigen because of its ability to directly bind with MHC-II class molecules followed by activation of a large proportion of T cells bearing specific Vβ-T cell receptors. Commonly associated with classic food poisoning, SEB has also been shown to induce toxic shock syndrome, and is also considered to be a potential biological warfare agent because it is easily aerosolized. In the present study, we assessed the ability of indole-3-carbinol (I3C) and one of its byproducts, 3,3'-diindolylmethane (DIM), found in cruciferous vegetables, to counteract the effects of SEB-induced activation of T cells in mice. Both I3C and DIM were found to decrease the activation, proliferation, and cytokine production by SEB-activated Vβ8(+) T cells in vitro and in vivo. Interestingly, inhibitors of histone deacetylase class I (HDAC-I), but not class II (HDAC-II), showed significant decrease in SEB-induced T cell activation and cytokine production, thereby suggesting that epigenetic modulation plays a critical role in the regulation of SEB-induced inflammation. In addition, I3C and DIM caused a decrease in HDAC-I but not HDAC-II in SEB-activated T cells, thereby suggesting that I3C and DIM may inhibit SEB-mediated T cell activation by acting as HDAC-I inhibitors. These studies not only suggest for the first time that plant-derived indoles are potent suppressors of SEB-induced T cell activation and cytokine storm but also that they may mediate these effects by acting as HDAC inhibitors.
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Philip B
authors.initials: PB
authors.lastname: Busbee
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA. Electronic address: prakash@mailbox.sc.edu.
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Nagarkatti
mesh_terms: D000818:Animals; D004768:Enterotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004768:Enterotoxins; D056572:Histone Deacetylase Inhibitors; D007211:Indoles; C031818:enterotoxin B, staphylococcal; C016517:indole-3-carbinol; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1; C016392:3,3'-diindolylmethane
keywords: 3,3′-Diindolylmethane; 3,3′-diindolylmethane; DIM; Epigenetic regulation; HDAC; HDAC-I; HDAC-II; Histone deacetylase; I3C; Indole-3-carbinol; Inflammation; MC; MC1568; MG; MGCD0103; SEB; Staphylococcal enterotoxin B; TSA; class I histone deacetylase; class II histone deacetylase; histone deacetylase; indole-3-carbinol; staphylococcal enterotoxin B; trichostatin A