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Time-dependent effect of LPS on PGE2 and TNF- production by rat glial brain culture: influence of COX and cytokine inhibitors

Department of Clinical Pharmacology, Ben Gurion University of the Negev, Beer Sheva, Israel

A.N. Azab

Department of Clinical Pharmacology, Ben Gurion University of the Negev, Beer Sheva, Israel

J. Kaplanski

Department of Clinical Pharmacology, Ben Gurion University of the Negev, Beer Sheva, Israel, jacobk{at}bgumail.bgu.ac.il

This study was undertaken to investigate the effect of lipopolysaccharide (LPS) stimulation on the time course of prostaglandin E₂ (PGE) and tumor necrosis factor alpha (TNF-) production by rat glial brain culture. A concentration of ²10 µg/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- production was tested. Stimulation of rat glial cells with LPS resulted in different time-dependent production patterns of PGE₂ and TNF. The time course of TNF- 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- levels, while INDO caused a greater elevation in TNF- levels. These results may cast further light on the LPS-induced production of PGE₂ and TNF- by rat glial cell cultures and the relation between the two systems.

Journal of Endotoxin Research, Vol. 6, No. 5, 377-381 (2000)
DOI: 10.1177/09680519000060050801


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