Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Interleukin-1 beta posttranslational processing - Exploration of P2X(7) receptor involvement
Autore:
Perregaux, DG; Labasi, J; Laliberte, R; Stam, E; Solle, M; Koller, B; Griffiths, R; Gabel, CA;
Indirizzi:
Pfizer Global Res & Dev, Dept Resp Allergy Immunol Inflammat & Infect Dis,Groton, CT 06340 USA Pfizer Global Res & Dev Groton CT USA 06340 fect Dis,Groton, CT 06340 USA Univ N Carolina, Dept Med, Chapel Hill, NC USA Univ N Carolina Chapel Hill NC USA rolina, Dept Med, Chapel Hill, NC USA
Titolo Testata:
DRUG DEVELOPMENT RESEARCH
fascicolo: 2-3, volume: 53, anno: 2001,
pagine: 83 - 90
SICI:
0272-4391(200106/07)53:2-3<83:IBPP-E>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXTRACELLULAR ATP; IL-1-BETA RELEASE; MICROGLIAL CELLS; HUMAN-MONOCYTES; HUMAN MACROPHAGES; PLASMA-MEMBRANES; P-2Z RECEPTOR; IN-VITRO; APOPTOSIS; ACTIVATION;
Keywords:
P2X(7) receptor; interleukin-1; inflammation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Gabel, CA Pfizer Global Res & Dev, Dept Resp Allergy Immunol Inflammat & Infect Dis,Groton, CT 06340 USA Pfizer Global Res & Dev Groton CT USA 06340roton, CT 06340 USA
Citazione:
D.G. Perregaux et al., "Interleukin-1 beta posttranslational processing - Exploration of P2X(7) receptor involvement", DRUG DEV R, 53(2-3), 2001, pp. 83-90

Abstract

Cultured monocytes and macrophages stimulated with LPS produce large quantities of prointerleukin (IL)-1 beta, but release little mature cytokine to the medium. The efficiency at which the procytokine is converted to its active 17 kDa species and released extracellularly is enhanced by treating cytokine-producing cells with a secretion stimulus such as ATP or nigericin. Alterations to the composition of the intracellular ionic environment, including a necessary K+ efflux, accompany the stimulus-induced secretory process. Cell death also accompanies stimulus-induced IL-1 posttranslational processing and human monocytes treated with ATP generate and release mature caspase-1. ATP-treated monocytes achieve a swollen morphology and do not produce mature caspase-3; these traits are uncharacteristic of an apoptotic mechanism. Stimulus-induced secretion of IL-1 beta is disrupted by substitutionof medium Cl- with chaotropic anions such as l(-) and by numerous anion transport inhibitors. These pharmacological agents block processing independently of the nature of the secretion stimulus, suggesting that a common downstream mechanism is engaged. Although sufficient to activate, the P2X(7) receptor (P2X(7)R) is not a necessary element of the secretory mechanism. KN-62, an antagonist of P2X7R function, inhibits ATP-induced IL-1 beta posttranslational processing but does not inhibit processing induced by nigericin. Likewise, LPS-activated peritoneal macrophages isolated from P2X(7)R-deficient mice respond to nigericin and produce mature 17 kDa IL-1 beta. On the other hand, the receptor-deficient macrophages, in contrast to their wild-type counterparts, do not respond to ATP. These findings highlight the unusual secretory requirements of IL-1 and demonstrate that P2X7R activation represents one mechanism by Which cytokine posttranslational processing can beinitiated. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 04:07:52