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Titolo:
SYNERGY BETWEEN TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1-BETA ININDUCING TRANSCRIPTIONAL DOWN-REGULATION OF MUSCARINIC M(2) RECEPTOR GENE-EXPRESSION - INVOLVEMENT OF PROTEIN-KINASE A AND CERAMIDE PATHWAYS
Autore:
HADDAD EB; ROUSELL J; LINDSAY MA; BARNES PJ;
Indirizzi:
UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,NATL HEART & LUNG INST,DEPT THORAC MED,DOVEHOUSE ST LONDON SW3 6LY ENGLAND UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,NATL HEART & LUNG INST,DEPT THORAC MED LONDON SW3 6LY ENGLAND
Titolo Testata:
The Journal of biological chemistry
fascicolo: 51, volume: 271, anno: 1996,
pagine: 32586 - 32592
SICI:
0021-9258(1996)271:51<32586:SBTAII>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTERFERON-GAMMA; MESSENGER-RNA; HUMAN FIBROBLASTS; CELL-LINE; TNF-ALPHA; ACTIVATION; CYTOKINES; BETA; MEDIATORS; IL-1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
E.B. Haddad et al., "SYNERGY BETWEEN TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1-BETA ININDUCING TRANSCRIPTIONAL DOWN-REGULATION OF MUSCARINIC M(2) RECEPTOR GENE-EXPRESSION - INVOLVEMENT OF PROTEIN-KINASE A AND CERAMIDE PATHWAYS", The Journal of biological chemistry, 271(51), 1996, pp. 32586-32592

Abstract

Stimulation of HEL 299 cells with tumor necrosis factor alpha (TNF-alpha) or interleukin 1 beta (IL-1 beta) had no effect on M(2) muscarinic receptor expression, However, the combination of Obese two cytokinesmarkedly down-regulated muscarinic M(2) receptor protein and mRNA expression and uncoupled M(2) receptors from adenylyl cyclase, There was no effect of TNF-alpha and IL-1 beta on the m2 muscarinic receptor mRNA stability, and nuclear run on assays showed reduced m2 receptor genetranscription, Sequential cytokine addition suggests that the synergyinvolves postreceptor events, Although the cAMP-dependent protein kinase inhibitor H8 provided a significant protection against receptor down-regulation, the protein kinase C inhibitor GF109203X had no effect. The ceramide analog C-2-ceramide (N-acetylsphingosine) was without effect on m2 receptor expression, However, a strong synergistic effect was demonstrated when cells were treated with the combination of C-2-ceramide and TNF-alpha or IL-1 beta. TNF-alpha and/or IL-1 beta combination also activated the 46- and 55-kDa c-Jun NH2-terminal protein kinases and to a lesser extent p42 and p44 mitogen-activated protein kinaseisoforms, Cycloheximide abolished the TNF-alpha and IL-1 beta effect,suggesting that de novo protein synthesis is required for receptor down-regulation, These results suggest that the TNF-alpha and IL-1 beta synergize to induce transcriptional down regulation of the M(2) muscarinic receptor, which seems to be mediated through activation of both ceramide and cAMP-dependent protein kinase pathways, Furthermore, theseresults suggest that M(2) receptor expression is under the control ofa cytokine network.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 13:24:44