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Titolo:
Pharmacological characterization of ATP- and LPS-induced IL-1 beta releasein human monocytes
Autore:
Grahames, CBA; Michel, AD; Chessell, IP; Humphrey, PPA;
Indirizzi:
Univ Cambridge, Dept Pharmacol, Glaxo Inst Appl Pharmacol, Cambridge CB2 1QJ, England Univ Cambridge Cambridge England CB2 1QJ col, Cambridge CB2 1QJ, England
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 8, volume: 127, anno: 1999,
pagine: 1915 - 1921
SICI:
0007-1188(199908)127:8<1915:PCOAAL>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
PURINERGIC P2Z RECEPTOR; EXTRACELLULAR ATP; INTERLEUKIN-1-BETA SECRETION; HUMAN MACROPHAGES; IN-VITRO; SEQUENCE; P2X(7); CELLS; ANTAGONISTS; INHIBITION;
Keywords:
P2X7; IL-1 beta; human monocytes; P2X(7) receptor; ATP; LPS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Chessell, IP Univ Cambridge, Dept Pharmacol, Glaxo Inst Appl Pharmacol, Tennis Court Rd, Cambridge CB2 1QJ, England Univ Cambridge Tennis Court Rd Cambridge England CB2 1QJ and
Citazione:
C.B.A. Grahames et al., "Pharmacological characterization of ATP- and LPS-induced IL-1 beta releasein human monocytes", BR J PHARM, 127(8), 1999, pp. 1915-1921

Abstract

1 We have utilized the human monocytic cell line, THP-1, and freshly isolated adherent human monocytes with the compounds pyridoxalphosphate-6-azophenyl-2',4'-disuphonic acid (PPADS), oxidized ATP, and 1-(N,O-bis{5-isoquinolinesufonyll}-N-methyl-L-tyrosyl)-4-phenylpiperazine (KN-62) to pharmacologically characterize the P2 receptor involved in ATP-induced release of interleukin 1 beta (IL-1 beta). We have also investigated the involvement of P2 receptors in lipopolysaccharide (LPS)induced IL-1 beta release from both cell types.2 ATP caused release of IL-1 beta from LPS primed THP-1 cells in both a time- and concentration-dependent manner, with a minimal effective ATP concentration of 1 mM. Stimulation of cells with 5 mM ATP resulted in detectable concentrations of IL-1 beta in cell supernatants within 30 min.3 The ATP analogue benzoylbenzoyl ATP (DBATP), a P2X(7) receptor agonist, was approximately 10 fold more potent than ATP at eliciting IL-1 beta release.4 KN-62 (1 mu M), PPADS (100 mu M) or oxidized ATP (100 uM) significantly inhibited 5 mM ATP-induced IL-1 beta release by 81, 90 and 66% respectively, but failed to significantly inhibit LPS-induced IL-1 beta release in bothTHP-1 cells and in freshly isolated human monocytes.5 In both THP-1 cells and freshly isolated human monocytes, addition of the ATP degrading enzyme apyrase (0.4 U ml(-1)) to cell supernatants prior toLPS activation failed to significantly inhibit the LPS-induced IL-1 beta release. In addition there was no correlation between extracellular ATP concentrations and IL-1 beta release in THP-1 cells when studied over a 6 h time period.6 In conclusion our data confirm the involvement of P2X(7) receptors in ATP-induced IL-1 beta release in human monocytes. However no evidence was obtained which would support the involvement of tither endogenous ATP release or P2X(7) receptor activation as the mechanism by which LPS-induces IL-1 beta release in either the THP-1 cell line or in freshly isolated human monocytes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 09:51:18