TY - JOUR T1 - 3,3'-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 JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.115.226563 SP - jpet.115.226563 AU - David Michael Elliott AU - Mitzi Nagarkatti AU - Prakash S Nagarkatti Y1 - 2016/01/01 UR - http://jpet.aspetjournals.org/content/early/2016/01/27/jpet.115.226563.abstract N2 - 3,3'-diindolylmethane (DIM) is natural indole found in cruciferous vegetables that 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 pre-treatment of mice with DIM led to attenuation of SEB-induced inflammation in the lungs, vascular leak, and IFN-γ 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 following 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, utilized miR-222. Collectively, these studies demonstrate for the first time that DIM treatment attenuates SEB-induced acute lung injury and may do so through the induction of microRNAs that promote apoptosis and cell cycle arrest in SEB-activated T cells. ER -