Many studies have shown that the pharmacological effects of
resveratrol, a phytoalexin polyphenolic compound, include protective effects against
cancer and
inflammation as well as enhancement of stress resistance. In this study, we examined whether
resveratrol affected the phagocytosis of bacteria by macrophages and the activation of the
transcription factor NF-kappaB after stimulation with or without the
ligand FSL-1 for
Toll-like receptor 2 (TLR2). Phagocytosis of Escherichia coli and of Staphylococcus aureus by THP-1 cells and RAW264.7 cells was inhibited by
resveratrol in a dose-dependent manner regardless of stimulation with FSL-1. The
NF-kappaB activity in HEK293 cells stably expressing TLR2 was also inhibited by
resveratrol after stimulation with FSL-1.
Resveratrol also inhibited both the translocation of p65 of
NF-kappaB into nuclei in the transfectant and
tumor necrosis factor alpha production by THP-1 cells or RAW264.7 cells. It has recently been reported that TLR-mediated signaling pathways lead to the upregulation of mRNAs of phagocytic receptors, including
scavenger receptors and
C-type lectin receptors. This study also demonstrated that FSL-1 induced the upregulation of mRNAs of phagocytic receptors such as macrophage scavenger receptor-1, CD36,
DC-SIGN, and
Dectin-1 and that the FSL-1-induced upregulation of their mRNAs was inhibited by
resveratrol. In addition, it was found that the expression of
DC-SIGN in HEK293 cells stably expressing
DC-SIGN was reduced by
resveratrol and that the phagocytic activity was significantly inhibited by
resveratrol. Thus, this study suggests that
resveratrol inhibited bacterial phagocytosis by macrophages by downregulating the expression of phagocytic receptors and
NF-kappaB activity.