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Titolo:
Therapeutic effects of cysteine protease inhibition in allergic lung inflammation: Inhibition of allergen-specific T lymphocyte migration
Autore:
Layton, GT; Harris, SJ; Bland, FA; Lee, SR; Fearn, S; Kaleta, J; Wood, ML; Bond, A; Ward, G;
Indirizzi:
British Biotech Pharmaceut PLC, Oxford OX4 5LY, England British Biotech Pharmaceut PLC Oxford England OX4 5LY d OX4 5LY, England Univ Southampton, CNS, Inflammat Grp, Southampton SO16 7PX, Hants, EnglandUniv Southampton Southampton Hants England SO16 7PX 6 7PX, Hants, England NAEJA Pharmaceut Inc, Edmonton, AB T6E 5V2, Canada NAEJA Pharmaceut Inc Edmonton AB Canada T6E 5V2 onton, AB T6E 5V2, Canada
Titolo Testata:
INFLAMMATION RESEARCH
fascicolo: 8, volume: 50, anno: 2001,
pagine: 400 - 408
SICI:
1023-3830(200108)50:8<400:TEOCPI>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
ASTHMATIC AIRWAY INFLAMMATION; COLONY-STIMULATING FACTOR; CATHEPSIN-B; MATRIX METALLOPROTEINASE-9; EOSINOPHIL PEROXIDASE; ANTIGEN PRESENTATION; INVARIANT CHAIN; IN-VITRO; CELLS; RESPONSES;
Keywords:
cathepsins; allergy; lymphocytes; therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Layton, GT British Biotech Pharmaceut PLC, Watlington Rd, Oxford OX4 5LY, England British Biotech Pharmaceut PLC Watlington Rd Oxford England OX4 5LY
Citazione:
G.T. Layton et al., "Therapeutic effects of cysteine protease inhibition in allergic lung inflammation: Inhibition of allergen-specific T lymphocyte migration", INFLAMM RES, 50(8), 2001, pp. 400-408

Abstract

Objective and design: We have evaluated the effects of the broad-spectrum cysteine protease inhibitor E64 on allergic lung inflammation in the mouse ovalbumin model of human asthma. We have also characterised membrane-associated cathepsin enzyme activity on a range of cell types. Materials: Balb/C mice, E64 and CA074. various cell lines. Treatment: E64 was administered by subcutaneous minipump into ovalbumin-sensitised mice prior to intranasal ovalbumin challenge. The effect of E64 onovalbumin-induced inflammation in vivo and ovalbumin-specific T cell proliferation in vitro and ex vivo was examined. Membrane-associated cathepsin activity on various cell types was measured. Results: E64 treatment (0.36-0.48 mg/day) led to a significant reduction in eosinophil numbers and lung weights in the mouse model. Histological examination of lungs confirmed the anti-inflammatory effect. E64 greatly reduced ovalbumin-specific T cell numbers in the lymph nodes draining the lung following intranasal challenge whilst an accumulation of these T cells was found in the 'priming' lymph nodes. An analysis of various cells involved in lymphocyte priming and migration revealed that monocytes. dendritic cells and endothelial cells express high levels of membrane-associated cathepsin Bactivity. Conclusions: Since E64 is not cell permeable and does not inhibit antigen-induced T cell proliferation in vitro or in vivo., the data indicate that membrane-associated cysteine proteases. possibly cathepsin B. may regulate Tlymphocyte migration in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 19:25:01