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Titolo:
IFN-GAMMA PRIMING OF MONOCYTES ENHANCES LPS-INDUCED TNF PRODUCTION BYAUGMENTING BOTH TRANSCRIPTION AND MESSENGER-RNA STABILITY
Autore:
HAYES MP; FREEMAN SL; DONNELLY RP;
Indirizzi:
US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,HFM-508,1401 ROCKVILLE PIKE ROCKVILLE MD 20852
Titolo Testata:
Cytokine
fascicolo: 5, volume: 7, anno: 1995,
pagine: 427 - 435
SICI:
1043-4666(1995)7:5<427:IPOMEL>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA-GENE; MURINE PERITONEAL-MACROPHAGES; NF-KAPPA-B; MESSENGER-RNA; INTERFERON-GAMMA; PROTEIN-KINASE; CYCLIC-AMP; MONONUCLEAR PHAGOCYTES; FACTOR CACHECTIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
59
Recensione:
Indirizzi per estratti:
Citazione:
M.P. Hayes et al., "IFN-GAMMA PRIMING OF MONOCYTES ENHANCES LPS-INDUCED TNF PRODUCTION BYAUGMENTING BOTH TRANSCRIPTION AND MESSENGER-RNA STABILITY", Cytokine, 7(5), 1995, pp. 427-435

Abstract

The induction of cytokine expression in monocytes/macrophages by bacterial endotoxin or lipopolysaccharide is a critical, highly regulated host defence response. The augmentation of LPS responses by interferongamma (IFN-gamma), referred to as priming, is weil established. However, the mechanism(s) by which priming occurs is poorly defined. Using tumour necrosis factor (TNF) induction as a model, experiments were designed to analyse in detail the printing effect on the LPS response inhuman monocytes. Priming by IFN-gamma was primarily manifested at thelevel of TNF mRNA accumulation. IFN-gamma pre-treatment affected the magnitude rather than the sensitivity of the LPS response. Priming occurred after several hours of treatment, and the primed state was induced by either IFN-gamma or GM-CSF, but not M-CSF. Primed monocytes transcribed TNF mRNA at a higher rate than freshly isolated monocytes uponactivation with LPS. The increased transcriptional rate correlated with a marked increase in nuclear factor-kappa B activity in these cellsas determined by electrophoretic mobility shift assay using a consensus NF-kappa B oligonucleotide. An additional significant finding was that TNF mRNA induced in primed cells was much more stable than in unprimed cells (T1/2 increased 6-8-fold). Consistent with the increased mRNA stability, the duration of mRNA accumulation was longer following LPS stimulation in primed monocytes, in addition to being of greater magnitude. Finally, primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89. H-89 substantially suppressedLPS-induced TNF mRNA accumulation in unprimed cells, but had no effect on primed monocytes following LPS stimulation. These results demonstrate that priming amplifies LPS-inducible TNF expression by increasingboth transcription and mRNA stability. (C) 1995 Academic Press Limited.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/07/20 alle ore 21:23:58