title: Time-dependent effect of LPS on PGE2 and TNF-alpha production by rat glial brain culture: influence of COX and cytokine inhibitors.
abstract: This study was undertaken to investigate the effect of lipopolysaccharide (LPS) stimulation on the time course of prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNF-alpha) production by rat glial brain culture. A concentration of 10 microg/ml LPS from Escherichia coli was used as stimulation treatment. The effect of pentoxifylline (PXF), nimesulide (NIM), indomethacin (INDO) and dexamethasone (DEX) on the regulation of PGE2 and TNF-alpha production was tested. Stimulation of rat glial cells with LPS resulted in different time-dependent production patterns of PGE2 and TNF-alpha The time course of TNF-alpha elevation was short, reaching its peak at 6 h post LPS and decreasing to undetectable levels after 24 h. On the other hand, the time course of PGE2 elevation was longer, starting at 6 h post LPS treatment and increasing 100-fold compared with basal levels, 24 h post LPS exposure. The COX inhibitors (NIM and INDO) and DEX were found to inhibit the LPS-induced elevation in PGE2 production, while PXF lacked such an inhibitory effect. Furthermore, NIM, DEX and PXF were found to reduce the LPS-induced elevation in TNF-alpha levels, while INDO caused a greater elevation in TNF-alpha levels. These results may cast further light on the LPS-induced production of PGE2 and TNF-alpha by rat glial cell cultures and the relation between the two systems.
authors.affiliation: Department of Clinical Pharmacology, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Shemi
authors.forename: A N
authors.initials: AN
authors.lastname: Azab
authors.forename: J
authors.initials: J
authors.lastname: Kaplanski
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D015232:Dinoprostone; D010431:Pentoxifylline; C012655:nimesulide; D007213:Indomethacin