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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{sup +} 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  More>>
Publication Date:
Jan 01, 2014
Product Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 274; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Subject:
60 APPLIED LIFE SCIENCES; INDOLES; INFLAMMATION; LYMPHOKINES; MESSENGER-RNA; MICE; POISONING; RECEPTORS; STAPHYLOCOCCUS; TOXICITY; TOXINS; VEGETABLES
OSTI ID:
22285551
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0041-008X; CODEN: TXAPA9; Other: PII: S0041-008X(13)00470-5; TRN: US14R3184106978
Availability:
Available from http://dx.doi.org/10.1016/j.taap.2013.10.022
Submitting Site:
USN
Size:
page(s) 7-16
Announcement Date:
Dec 11, 2014

Citation Formats

Busbee, Philip B., Nagarkatti, Mitzi, and Nagarkatti, Prakash S., E-mail: prakash@mailbox.sc.edu. Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression. United States: N. p., 2014. Web. doi:10.1016/J.TAAP.2013.10.022.
Busbee, Philip B., Nagarkatti, Mitzi, & Nagarkatti, Prakash S., E-mail: prakash@mailbox.sc.edu. Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression. United States. doi:10.1016/J.TAAP.2013.10.022.
Busbee, Philip B., Nagarkatti, Mitzi, and Nagarkatti, Prakash S., E-mail: prakash@mailbox.sc.edu. 2014. "Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression." United States. doi:10.1016/J.TAAP.2013.10.022. https://www.osti.gov/servlets/purl/10.1016/J.TAAP.2013.10.022.
@misc{etde_22285551,
title = {Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression}
author = {Busbee, Philip B., Nagarkatti, Mitzi, and Nagarkatti, Prakash S., E-mail: prakash@mailbox.sc.edu}
abstractNote = {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{sup +} 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. - Highlights: • I3C and DIM reduce SEB-induced T cell activation and inflammatory cytokines. • Inhibiting class I HDACs reduces T cell activation and inflammatory cytokines. • Inhibiting class II HDACs increases T cell activation and inflammatory cytokines. • I3C and DIM selectively reduce mRNA expression of class I HDACs. • Novel use and mechanism to counteract SEB with I3C and DIM.}
doi = {10.1016/J.TAAP.2013.10.022}
journal = {Toxicology and Applied Pharmacology}
issue = {1}
volume = {274}
journal type = {AC}
place = {United States}
year = {2014}
month = {Jan}
}