Resveratrol is a poly phenolic compound found selleck catalog in a large number of plant species that are components of human diet, including mulberries, peanuts, grapes and red wine. Accumulating evidence suggests that resveratrol may exert a protective effect in the CNS under pathological conditions, and that resveratrol is associated Inhibitors,Modulators,Libraries with reduced risks of cardi ovascular disease, cancer, diabetes and AD. Resveratrol has also been proposed to be an anti inflam matory molecule. In glial cells, resveratrol has been reported to inhibit LPS induced production of NO and TNF a by the murine microglia cell line N9, to inhibit prostaglandin E2 and free radical produc tion by rat primary microglia, and to inhibit NO and PGE2 by the rat astroglial cell line C6.

Micro glia and astrocytes are two cell types with different bio logical characteristics and functions in the CNS, it is not clear Inhibitors,Modulators,Libraries if there are differences between these cells in response to LPS or if resveratrol inhibits the inflamma tory responses of these cells to LPS through similar mechanisms. In the present study, we first examined the expression of various proinflammatory cytokines and of iNOS by murine microglia and astrocytes in response to LPS, and the signaling mole cules involved. We then determined the effects of resveratrol on microglial Inhibitors,Modulators,Libraries cell and astrocyte activation by LPS, and explored the underlying key signaling Inhibitors,Modulators,Libraries molecules. Methods Materials Resveratrol, LPS and MTT were obtained from Sigma. PD98059, SP600125, SB203580, sulfa salazine and curcumin were from Calbiochem.

Antibodies against both phosphorylated and unphosphorylated extracellular sig nal regulated kinases, p38, c jun N terminal kinase were obtained from Cell Signaling Tech nology. Dual Luciferase Reporter Assay System was from Promega Corporation. LightShift Chemiluminescent Inhibitors,Modulators,Libraries EMSA kit was from Pierce. DMEM was pur chased from Gibco BRL. Fetal bovine serum was from Hyclone. All other reagents were obtained from Sigma Aldrich unless otherwise described. Glial cell cultures Primary mouse microglia were isolated and purified from whole brain of newborn C57BL 6 mice as previously described. Briefly, brain tissues were minced into small pieces. Cells were separated by trypsinization and cultured in 75 cm2 tissue kinase inhibitor Erlotinib culture flasks with DMEM med ium containing 10% FBS, 100 umol L non essential amino acids, 5 ug mL insulin, 100 U mL penicillin and 100 ug mL streptomycin. When cells grew to confluence, flasks were shaken overnight to loosen microglia and oligodendrocytes from the more adherent astrocytes. These less adherent cells were plated for 1 h and then lightly shaken to separate oligodendrocytes from the more adherent microglia. Microglia were seeded in cell culture plates for future use.