title: 3,39-Diindolylmethane Ameliorates Staphylococcal Enterotoxin  B–Induced Acute Lung Injury through Alterations in the  Expression of MicroRNA that Target Apoptosis and Cell-Cycle  Arrest in Activated T Cells.
abstract: 3,39-Diindolylmethane (DIM), a natural indole found in cruciferous vegetables, has significant anti-cancer and anti-inflammatory properties. In this current study, we investigated the effects of DIM on acute lung injury (ALI) induced by exposure to staphylococcal enterotoxin B (SEB). We found that pretreatment of mice with DIM led to attenuation of SEB-induced inflammation in the lungs, vascular leak, and IFN-g secretion. Additionally, DIM could induce cell-cycle arrest and cell death in SEB-activated T cells in a concentration-dependent manner. Interestingly, microRNA (miRNA) microarray analysis uncovered an altered miRNA profile in lung-infiltrating mononuclear cells after DIM treatment of SEB-exposed mice. Moreover, computational analysis of miRNA gene targets and regulation networks indicated that DIM alters miRNA in the cell death and cell-cycle progression pathways. Specifically, DIM treatment significantly downregulated several miRNA and a correlative increase associated gene targets. Furthermore, overexpression and inhibition studies demonstrated that DIM-induced cell death, at least in part, used miR-222. Collectively, these studies demonstrate for the first time that DIM treatment attenuates SEB-induced ALI and may do so through the induction of microRNAs that promote apoptosis and cell-cycle arrest in SEB-activated T cells.
authors.forename: David M
authors.initials: DM
authors.lastname: Elliott
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Nagarkatti
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D019559:Capillary Leak Syndrome / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004768:Enterotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D020556:Neutrophil Infiltration / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D004768:Enterotoxins; D007211:Indoles; C546123:MIRN222 microRNA, mouse; D035683:MicroRNAs; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma; C016392:3,3'-diindolylmethane
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