Resveratrol protects experimental Staphylococcus aureus enterotoxin B (SEB)-induced acute liver injury (ALI) by regulating microRNAs associated with myeloid-derived suppressor cells

Abstract

Abstract Resveratrol (RES) possesses anti-inflammatory, anticancer, and antioxidant properties. Because of anti-inflammatory property of RES, we investigated whether RES can attenuate Staphylococcal enterotoxin B (SEB)-induced acute liver injury (ALI) in mice. SEB exposure causes food poisoning as well as toxic shock syndrome leading to mortality. We observed that SEB caused ALI in female mice and there was an increase in enzyme aspartate transaminase (AST) levels, induction of inflammatory cytokines, and massive infiltration of immune cells into the liver. RES (50 mg/kg body weight) treatment attenuated SEB-induced ALI and significantly decreased AST levels, inflammatory cytokines and chemokines, and cellular infiltration in the liver. Interestingly, RES treatment led to an increase in myeloid derived suppressor cells (MDSC) in SEB-immunized mice. Upon examination of microRNAs (miRs) profile of liver infiltrating mononuclear cells (MNCs), there was marked change in microRNA expression profile in mice exposed to SEB and treated with RES. Specifically, there was a decrease in the expression of miR-130a and miR-185 in MNCs from SEB+RES treated mice when compared to SEB+VEH treated group. Furthermore, there was an inverse relationship between miR-130a and miR-185 with CSF-1 gene expression in liver MNCs. The data presented demonstrate for the first time that RES can effectively attenuate SEB-induced ALI by inducing the proliferation of MDSC. In summary, the beneficial effects of RES may be mediated by changes in miRs regulating pathways leading to the generation of immunosuppressive cells and/or production of anti-inflammatory cytokines suppressing SEB-induced ALI.