Resveratrol modulates phagocytosis of bacteria through an NF-kappaB-dependent gene program.
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.
Iyori
Mitsuhiro
M
Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Nishi 7, Kita 13, Kita-ku, Sapporo 060-8586, Japan.
Kataoka
Hideo
H
Shamsul
Haque Mohammad
HM
Kiura
Kazuto
K
Yasuda
Motoaki
M
Nakata
Takashi
T
Hasebe
Akira
A
Shibata
Ken-ichiro
K
D000818:Animals; D002460:Cell Line; D004926:Escherichia coli / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013211:Staphylococcus aureus / Q000276:immunology; D013267:Stilbenes / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism
D016328:NF-kappa B; D011971:Receptors, Immunologic; D013267:Stilbenes; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D000077185:Resveratrol