The role of surface receptor stimulation on the cytotoxicity of resveratrol to macrophages.
The present work has evaluated the role of lipopolysaccharide (LPS) stimulation and of TLR4 receptors on the cytotoxicity of resveratrol (RES), a polyphenolic stilbene component of red wine, in TLR4-bearing (i.e., RAW 264.7) and TLR4-deficient (i.e., 10ScNCr/23) macrophages. Based on the results of the MTT assay, DNA fragmentation analysis, and scanning electron microscopic examination, cell stimulation with LPS was found to maintain the viability of, attenuate DNA fragmentation in, and preserve normal morphology of TLR4-proficient macrophages exposed to RES. In contrast, LPS failed to spare TLR4-deficient macrophages from the deleterious effects of RES. Moreover, while LPS treatment conferred protection from RES toxicity in TLR4-bearing macrophages, this stilbene inhibited the production of nitric oxide by stimulated cells in a concentration-dependent fashion. It is therefore likely that the cytotoxic effects of RES towards non-stimulated macrophages and the propensity of RES to inhibit nitric oxide production by activated macrophages are both contributing, at least in part, to the anti-inflammatory activity of this natural product.
Department of Pharmaceutical Sciences, St. John's University, Jamaica, NY 11439, USA.
Vijayalaxmi
V
Radkar
Cesar
C
Lau-Cam
Diane
D
Hardej
Blase
B
Billack
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D053938:DNA Fragmentation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000648:ultrastructure; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009573:Nitrites / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics
D000972:Antineoplastic Agents, Phytogenic; D003470:Culture Media; D008070:Lipopolysaccharides; D009573:Nitrites; D011956:Receptors, Cell Surface; D013267:Stilbenes; D013778:Tetrazolium Salts; D013844:Thiazoles; D051197:Toll-Like Receptor 4; C022616:thiazolyl blue; D000077185:Resveratrol