Abstract
Resveratrol (RES) is a polyphenolic compound found abundantly in plant products including red grapes, peanuts, and mulberries. Because of potent anti-inflammatory properties of RES, we investigated whether RES can protect from Staphylococcal enterotoxin B (SEB)-induced acute liver injury in mice. SEB is a potent super antigen that induces robust inflammation and releases inflammatory cytokines that can be fatal. We observed that SEB caused acute liver injury in mice with increases in enzyme aspartate transaminase (AST) levels, and massive infiltration of immune cells into the liver. Treatment with RES (100 mg/kg body weight) attenuated SEB-induced acute liver injury, as indicated by decreased AST levels and cellular infiltration in the liver. Interestingly, RES treatment increased the number of myeloid derived suppressor cells (MDSCs) in the liver. RES treatment led to alterations in the microRNA (miR) profile in liver mononuclear cells (MNCs) of mice exposed to SEB, and pathway analysis indicated these miRs targeted many inflammatory pathways. Of these, we identified miR-185, which was down-regulated by RES, to specifically target Colony Stimulating Factor (CSF1) using transfection studies. Moreover, the levels of CSF1 were significantly increased in RES-treated SEB mice. Because CSF1 is critical in MDSC induction, our studies suggest that RES may induce MDSCs by down-regulating miR-185 leading to increase the expression of CSF1. The data presented demonstrate for the first time that RES can effectively attenuates SEB-induced acute liver injury and that this may result from its action on miRs and induction of MDSCs.
Highlights
Resveratrol (RES: trans-3,5,4 -trihydroxystilbene) is a nonflavonoid polyphenolic compound found abundantly in a large number of plant products including red grapes, red wine, peanut, mulberries and the like (Jang et al, 1997; Jang and Surh, 2001)
Inflammation was observed in the liver Staphylococcal enterotoxin B (SEB)+RES mice, the level of inflammation was significantly reduced, when compared to liver tissues from mice treated with SEB+VEH (Figure 1A,g,h)
We investigated whether RES, which is wellknown for its potent anti-inflammatory property, can protect SEB-induced inflammation in liver and attenuate acute liver injury
Summary
Resveratrol (RES: trans-3,5,4 -trihydroxystilbene) is a nonflavonoid polyphenolic compound found abundantly in a large number of plant products including red grapes, red wine, peanut, mulberries and the like (Jang et al, 1997; Jang and Surh, 2001). RES has been the focus of many studies, including our own laboratory, for its pharmacological and beneficial properties on a wide range of diseases, including cardiovascular, autoimmune, neurological, and hepatic (Baur and Sinclair, 2006; Singh et al, 2007a, 2011). We have previously shown the beneficial effects of RES on autoimmune and inflammatory diseases (Singh et al, 2007a, 2010, 2011; Singh U.P. et al, 2012). Due to the wide-ranging beneficial effects of RES, it has recently been introduced as a nutritional supplement in the market (Aschemann-Witzel and Grunert, 2015) and presently, it is being used extensively, in United States and worldwide
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