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Effect of platelet activating factor antagonist WEB 2086 on the production of TNF from murine peritoneal macrophages
1Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai.
Abstract:
In the present study the effect of platelet activating factor (PAF) antagonist WEB 2086 on the production of tumor necrosis factor (TNF) from primed murine peritoneal macrophages was investigated. At 10(-6) and 10(-5) mol/L, WEB 2086 was found to significantly inhibit LPS induced TNF production from macrophages by activated thioglycollate solution. WEB 2086 inhibition of TNF release began 4 h after LPS stimulation and lasted 22 h with a peek at 16 h. The results showed that PAF might play an important role in the production of TNF. Four methods were compared in the bioassay of TNF. The data demonstrated that L-929 cells treated with actinomycin D and sodium fluoride were the most sensitive for the assay of TNF. This method was employed in this study.
Insights
Platelet activating factor (PAF) antagonist WEB 2086 significantly inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production in macrophages. This suggests PAF plays a key role in TNF production.
Area of Science:
- Immunology
- Pharmacology
Background:
- Tumor necrosis factor (TNF) is a key cytokine in inflammatory responses.
- Platelet activating factor (PAF) is implicated in various inflammatory processes.
- Understanding the interplay between PAF and TNF is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the effect of the PAF antagonist WEB 2086 on TNF production.
- To determine the role of PAF in lipopolysaccharide (LPS)-induced TNF release from macrophages.
Main Methods:
- Murine peritoneal macrophages were primed and stimulated with LPS.
- The impact of WEB 2086 on TNF production was assessed at different concentrations (10(-6) and 10(-5) mol/L).
- TNF bioassay was optimized using L-929 cells treated with actinomycin D and sodium fluoride.
Main Results:
- WEB 2086 significantly inhibited LPS-induced TNF production.
- Inhibition of TNF release by WEB 2086 was observed starting 4 hours post-stimulation, peaking at 16 hours, and lasting for 22 hours.
- The optimized bioassay method demonstrated high sensitivity for TNF detection.
Conclusions:
- PAF antagonist WEB 2086 effectively suppresses TNF production.
- These findings highlight a significant role for PAF in the regulation of TNF release.
- The developed bioassay provides a sensitive method for TNF quantification.