Staphylococcal enterotoxin B (SEB) is a potent
superantigen capable of inducing
inflammation characterized by robust immune cell activation and proinflammatory
cytokine release. Exposure to SEB can result in
food poisoning as well as fatal conditions such as
toxic shock syndrome. In the current study, we investigated the effect of natural
indoles including
indole-3-carbinol (I3C) and
3,3'-diindolylmethane (DIM) on SEB-mediated liver injury. Injection of SEB into D-
galactosamine-sensitized female C57BL/6 mice resulted in liver injury as indicated by an increase in
enzyme aspartate transaminase (AST) levels, induction of inflammatory
cytokines, and massive infiltration of immune cells into the liver. Administration of I3C and DIM (40 mg/kg), by intraperitonal injection, attenuated SEB-induced acute liver injury, as evidenced by decrease in AST levels, inflammatory
cytokines and cellular infiltration in the liver. I3C and DIM triggered apoptosis in SEB-activated T cells primarily through activation of the intrinsic mitochondrial pathway. In addition, inhibitor studies involving
caspases revealed that I3C and DIM-mediated apoptosis in these activated cells was dependent on
caspase-2 but independent of
caspase-8, 9 and 3. In addition, I3C and DIM caused a decrease in Bcl-2 expression. Both compounds also down-regulated miR-31, which directly targets
caspase-2 and influences apoptosis in SEB-activated cells. Our data demonstrate for the first time that
indoles can effectively suppress acute hepatic
inflammation caused by SEB and that this may be mediated by decreased expression of miR-31 and consequent caspase-2-dependent apoptosis in T cells.