Effect of indomethacin on the kinetics of tumour necrosis factor alpha release and tumour necrosis factor alpha gene expression by human blood monocytes
| Autor: | Elisabetta Pace, Mario Spatafora, Domenico D'amico, Daniela Volpes, M. Melis, Anna Maria Merendino, G. Chiappara |
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| Rok vydání: | 1991 |
| Předmět: |
Lipopolysaccharides
Transcription Genetic Lipopolysaccharide Neutrophils medicine.medical_treatment Indomethacin Prostaglandin In Vitro Techniques Pharmacology Dinoprostone Cyclooxygenase pathway chemistry.chemical_compound Gene expression medicine Humans RNA Messenger Tumor Necrosis Factor-alpha business.industry Monocyte Kinetics medicine.anatomical_structure Cytokine Gene Expression Regulation chemistry Immunology Indicators and Reagents Arachidonic acid Tumor necrosis factor alpha business |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1043-6618 |
| Popis: | Summary In this investigation we have examined the effects of indomethacin, an inhibitor of the cyclooxygenase pathway of arachidonic acid, upon the kinetics of the release of tumour necrosis factor alpha (TNF) and of the expression of TNF gene by lipopolysaccharide (LPS)-stimulated human blood monocytes (BM). Following stimulation of BM with LPS, TNF was released within 2 h, reached peak values at 8 h and declined at subsequent time-points (24 and 48 h). Indomethacin (10−5 m ) slightly stimulated the production of TNF at 2, 4, and 8 h and prevented the decline of TNF observed at 24 and 48 h. This effect was related to the persistence of TNF synthesis, as demonstrated by kinetics evaluation of the expression of TNF gene performed by dot-blot analysis. The effects of indomethacin on TNF release and TNF gene expression were due to the inhibition of endogenous prostaglandin (PG)E2 production. In the absence of indomethacin, PGE2 release by the LPS-stimulated BM began concomitantly with the decline of TNF production by the same cells under the same stimulus. Indomethacin completely blocked PGE2 release at any time-point. Exogenous PGE2 suppressed the release of TNF and the expression of TNF gene in a dose-dependent fashion. Exogenous PGE2 completely reversed the effects of indomethacin on TNF production at 24 h. These findings suggest that indomethacin may significantly alter the kinetics of TNF release and TNF gene expression by LPS-stimulated BM. These effects are related, at least in part, to the inhibition of the production of endogenous PGE2, an important self-driven regulatory factor of the kinetics of TNF production. |
| Databáze: | OpenAIRE |
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