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Titolo:
Stimulation of inflammatory responses in vitro and in vivo by lipophilic HMG-CoA reductase inhibitors
Autore:
Kiener, PA; Davis, PM; Murray, JL; Youssef, S; Rankin, BM; Kowala, MK;
Indirizzi:
Bristol Myers Squibb Co, Dept Immunol & Inflammat, Princeton, NJ 08543 USABristol Myers Squibb Co Princeton NJ USA 08543 t, Princeton, NJ 08543 USA Bristol Myers Squibb Co, Dept Cardiovasc Drug Discovery, Princeton, NJ 08543 USA Bristol Myers Squibb Co Princeton NJ USA 08543 y, Princeton, NJ 08543 USA
Titolo Testata:
INTERNATIONAL IMMUNOPHARMACOLOGY
fascicolo: 1, volume: 1, anno: 2001,
pagine: 105 - 118
SICI:
1567-5769(200101)1:1<105:SOIRIV>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
CORONARY-ARTERY DISEASE; HUMAN CELL-TYPES; MEVALONATE PATHWAY; IN-VITRO; CYTOKINE PRODUCTION; STEROL SYNTHESIS; MONOCYTIC CELLS; TISSUE-FACTOR; PRAVASTATIN; EXPRESSION;
Keywords:
inflammation; monocyte; leukocyte; HMG-CoA reductase; cytokine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Kiener, PA Bristol Myers Squibb Co, Dept Immunol & Inflammat, K14-09,PRI,POB 4000, Princeton, NJ 08543 USA Bristol Myers Squibb Co K14-09,PRI,POB 4000 Princeton NJ USA 08543
Citazione:
P.A. Kiener et al., "Stimulation of inflammatory responses in vitro and in vivo by lipophilic HMG-CoA reductase inhibitors", INT IMMUNO, 1(1), 2001, pp. 105-118

Abstract

The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyses the rate limiting step in cholesterol biosynthesis and is markedly inhibited by the statin family of drugs. The effect of statins on lipid lowering is clearly defined, bur the ability of the drugs to directly regulate inflammatory functions has not been well explored. In this report, we show that there are differences among the statins in their capacity to induce proinflammatory responses both in human monocytes in vitro, and in leukocytes in mice in vivo. Treatment of human monocytes with lipophilic statins alone stimulated the production of MCP-1, IL-8, TNF-alpha and IL-1 beta and markedly sensitized the cells to subsequent challenge with inflammatory agents. Lipophilic statins also increased the production of reactive oxygen speciesin monocytes. In contrast, pretreatment of cells with the hydrophilic pravastatin did not induce these heightened inflammatory responses. Furthermore, treatment of mice with lipophilic statins caused a markedly higher influxof leukocytes into the inflamed peritoneal cavity following challenge withthioglycollate. Overall, these results demonstrate that the lipophilic statins influence a regulatory pathway in monocytes that controls cytokine production and that the statins induce different pro-inflammatory responses both in vitro and in vivo. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 05:46:31