Time-dependent effect of LPS on PGE2 and TNF-alpha production by rat glial brain culture: influence of COX and cytokine inhibitors.
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.
Shemi
D
D
Department of Clinical Pharmacology, Ben Gurion University of the Negev, Beer Sheva, Israel.
Azab
A N
AN
Kaplanski
J
J
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*
D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D015232:Dinoprostone; D010431:Pentoxifylline; C012655:nimesulide; D007213:Indomethacin