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Temporally different stimulation of TNF-alpha and PGE2 release from GM-CSF-primed macrophages.
- Source :
-
Lymphokine research [Lymphokine Res] 1989 Fall; Vol. 8 (3), pp. 353-7. - Publication Year :
- 1989
-
Abstract
- Since granulocyte-macrophage colony-stimulating factor (GM-CSF) has previously been shown to activate macrophages, it was of particular interest to study its effect on synthesis and release of tumor necrosis factor-alpha (TNF-alpha). GM-CSF alone was incapable of activating murine peritoneal macrophages to TNF-alpha release. However, in response to lipopolysaccharide (LPS), GM-CSF was found to prime macrophages for enhanced TNF-alpha production. This priming effect was short-lived and was superseded by the contrary, an unresponsiveness to LPS. The suppressed response was due to a delayed production of prostaglandin E2 (PGE2) which did not affect GM-CSF-enhanced TNF-alpha gene transcription but blocked TNF-alpha production. When PGE2 synthesis was inhibited by indomethacin, the priming effect of GM-CSF was entirely reconstituted. Thus, GM-CSF initially primes for TNF-alpha and subsequently for PGE2 release which, taken together, may represent an autoregulatory feed-back system that could restrict macrophage activation.
- Subjects :
- Animals
Granulocyte-Macrophage Colony-Stimulating Factor
In Vitro Techniques
Kinetics
Macrophage Activation
Macrophages drug effects
Macrophages immunology
Macrophages metabolism
Mice
Mice, Inbred DBA
Colony-Stimulating Factors pharmacology
Dinoprostone metabolism
Growth Substances pharmacology
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0277-6766
- Volume :
- 8
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Lymphokine research
- Publication Type :
- Academic Journal
- Accession number :
- 2674560