Resveratrol enhances the effect of lipopolysacchride on human monocytes THP‐1 pro‐inflammatory cytokine expression

Resveratrol (Res) is a polyphenolic compound existing in grapes, red wine, and certain fruits that exhibits anti‐tumor and anti‐inflammatory properties. The anti‐inflammatory effect of Res at pharmacological concentrations of >25 μM have been reported, but not at a physiological concentration (~5 μM) normally absorbed through diet. In addition, the mechanisms of action remain largely unknown. We addressed these deficiencies using a cell‐based inflammatory model in vitro. A concentration‐dependent reduction in cell growth was observed in cultured human monocytes THP‐1 cells treated for 48 hours with Res that covered physiological and pharmacological concentrations (≤25 μM). Flow cytometry analysis indicated that 5 and 10 μM of Res induced cell cycle arrest at the S phase. At 25 μM, Res induced both G0/G1 arrest and apoptosis. These effects of Res correlated with up regulation of p53‐independent cyclin‐dependent kinase inhibitor 1A (CDKN1A) mRNA expression. More importantly, Res enhanced the lipopolysacchride (LPS, 10ng/mL)‐induced inflammatory markers IL‐1β, IL‐6, IL‐8, MCP‐1, COX‐2, and TNF‐α mRNA expression in a concentration‐dependent fashion. LPS binds to CD14/TLR4/MD2 receptor complex and promotes the secretion of pro‐inflammatory cytokines. These results suggested that Res exerts a concentration‐dependent effect on immune cell growth and responsiveness toward inflammatory stimuli. Grant Funding Source : U.S appropriated funds to USDA project number 1235‐51530‐052‐00