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Titolo:
INDUCTION OF CYCLO-OXYGENASE-2 BY CYTOKINES IN HUMAN CULTURED AIRWAY SMOOTH-MUSCLE CELLS - NOVEL INFLAMMATORY ROLE OF THIS CELL-TYPE
Autore:
BELVISI MG; SAUNDERS MA; HADDAD EB; HIRST SJ; YACOUB MH; BARNES PJ; MITCHELL JA;
Indirizzi:
NATL HEART & LUNG INST,IMPERIAL COLL MED,DOVEHOUSE ST LONDON SW3 6LY ENGLAND UNITED MED & DENT SCH,ST THOMAS HOSP,DEPT MED LONDON SE1 7EH ENGLAND NATL HEART & LUNG INST,IMPERIAL COLL SCH MED LONDON SW3 6LY ENGLAND ROYAL BROMPTON HOSP,DEPT ANAESTHESIA & CRIT CARE MED LONDON SW3 6NP ENGLAND
Titolo Testata:
British Journal of Pharmacology
fascicolo: 5, volume: 120, anno: 1997,
pagine: 910 - 916
SICI:
0007-1188(1997)120:5<910:IOCBCI>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
SYNTHETASE INHIBITOR OKY-046; PROSTAGLANDIN-H SYNTHASE-2; INDUCIBLE CYCLOOXYGENASE; INHALED PROSTAGLANDIN-E2; ALVEOLAR MACROPHAGES; MESSENGER-RNA; EXPRESSION; ASTHMA; LIPOPOLYSACCHARIDE; GENE;
Keywords:
PROSTAGLANDINS; AIRWAY SMOOTH MUSCLE; ASTHMA; CYTOKINES; CYCLO-OXYGENASE-2;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
M.G. Belvisi et al., "INDUCTION OF CYCLO-OXYGENASE-2 BY CYTOKINES IN HUMAN CULTURED AIRWAY SMOOTH-MUSCLE CELLS - NOVEL INFLAMMATORY ROLE OF THIS CELL-TYPE", British Journal of Pharmacology, 120(5), 1997, pp. 910-916

Abstract

1 Cyclo-oxygenase (COX) is the enzyme that converts arachidonic acid to prostaglandin H-2 (PGH(2)) which can then be further metabolized toprostanoids which modulate various airway functions. COX exists in atleast two isoforms. COX-1 is expressed constitutively, whereas COX-2 is expressed in response to pro-inflammatory stimuli. Prostanoids are produced under physiological and pathophysiological conditions by manycell types in the lung. However, the regulation of the different COX isoforms in human airway smooth muscle (HASM) cells has not yet been determined. 2 COX-1 and COX-2 protein were measured by Western blot analysis with specific antibodies for COX-1 and COX-2. COX-2 mRNA levels were assessed by Northern blot analysis by use of a COX-2 cDNA probe. COX activity was determined by measuring conversion of either endogenous or exogenous arachidonic acid to three metabolites, PGE(2), thromboxane B-2 or 6-ketoPGF(1 alpha) by radioimmunoassay.3 Under control culture conditions HASM cells expressed COX-1, but not COX-2, protein. However, a mixture of cytokines (interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) each at 10 ng ml(-1)) induced COX-2 mRNA expression, which was maximal at12 h and inhibited by dexamethasone (1 mu M; added 30 min before the cytokines). Furthermore, COX-2 protein was detected 24 h after the cytokine treatment and the expression of this protein was also inhibited by dexamethasone (1 mu M) and cyclohexamide (10 mu g ml(-1); added 30 min before the cytokines). 4 Untreated HASM cells released low or undetectable amounts of all COX metabolites measured over a 24 h period. Incubation of the cells with the cytokine mixture (IL-1 beta, TNF alpha, IFN gamma each at 10 ng ml(-1) for 24 h) caused the accumulation of PGE(2) and 6-keto-PGF(1 alpha). 5 In experiments where COX-2 metabolized endogenous stores of arachidonic acid, treatment of HASM cells withIL-1 beta in combination with TNF alpha caused a similar release of PGE(2) to that when the three cytokines were given in combination. 6 Inother experiments designed to measure COX-2 activity directly, cells were treated with cytokines for 24 h before fresh culture medium was added containing exogenous arachidonic acid (30 mu M for 15 min) after which PGE(2) was measured. IL-1 beta and TNF alpha increased COX-2 activity and an additional small increase was produced by the three cytokines in combination. 7 These findings suggest that the increased expression of COX-2 is intimately involved in the exaggerated release of prostanoids from HASM cells exposed to pro-inflammatory cytokines. Thesedata indicate a role for airway smooth muscle cells, in addition to their contractile function, as inflammatory cells involved in the production of mediators which may contribute to the inflammatory response seen in diseases such as asthma.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 18:10:12