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Titolo:
Functional effects of the inhibition of the cysteine protease activity of the major house dust mite allergen Der p 1 by a novel peptide-based inhibitor
Autore:
John, RJ; Rusznak, C; Ramjee, M; Lamont, AG; Abrahamson, M; Hewitt, EL;
Indirizzi:
Peptide Therapeut Ltd, Cambridge CB1 9PT, England Peptide Therapeut Ltd Cambridge England CB1 9PT mbridge CB1 9PT, England St Bartholomews & Royal London Sch Med & Dent, Acad Dept Resp Med, London E2 9JX, England St Bartholomews & Royal London Sch Med & Dent London England E2 9JX land Univ Lund, Dept Clin Biochem, Lund, Sweden Univ Lund Lund SwedenUniv Lund, Dept Clin Biochem, Lund, Sweden
Titolo Testata:
CLINICAL AND EXPERIMENTAL ALLERGY
fascicolo: 6, volume: 30, anno: 2000,
pagine: 784 - 793
SICI:
0954-7894(200006)30:6<784:FEOTIO>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYSTATIN-C ACTIVITY; CELLS IN-VITRO; EPITHELIAL-CELLS; PROTEINASE-INHIBITOR; DERMATOPHAGOIDES-PTERONYSSINUS; NEUTROPHIL ELASTASE; ESCHERICHIA-COLI; IGE; ALPHA-1-ANTITRYPSIN; PERMEABILITY;
Keywords:
CD23; cystatin; cysteine protease; Der p 1; epithelial permeability; inhibitor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Hewitt, EL Peptide Therapeut Ltd, Peterhouse Technol Pk,100 Fulbourn Rd, Cambridge CB1 9PT, England Peptide Therapeut Ltd Peterhouse Technol Pk,100 Fulbourn Rd Cambridge England CB1 9PT
Citazione:
R.J. John et al., "Functional effects of the inhibition of the cysteine protease activity of the major house dust mite allergen Der p 1 by a novel peptide-based inhibitor", CLIN EXP AL, 30(6), 2000, pp. 784-793

Abstract

Background The house dust mite (HDM) Dermatophagoides pteronyssinus is an important source of allergens, which can cause allergic conditions. The cysteine protease activity of Der p 1 may enhance the potency of this major mite allergen through cleavage of CD23 and CD25 from the surface of immune cells, IgE independent mast cell activation, increases in epithelial cell permeability and inactivation of an endogenous serine protease inhibitor. Inhibition of the enzymatic activity of Der p 1 may therefore be of therapeuticbenefit. Objective To examine the activity of PTL11028, a newly developed Der p 1 inhibitor, in a range of assays that directly or indirectly measure Der p 1 protease activity and to compare its activity to endogenous cysteine protease inhibitors. Methods The proteolytic activities of purified Der p 1 or HDM extract and inhibitory properties of PTL11028 were examined through cleavage of an artificial peptidyl substrate, cleavage of CD23 from human B cells and permeability studies on primary human bronchial epithelial cells. Results PTL11028 is a highly potent and specific Der p 1 inhibitor, being effective against both purified protease and Der p 1 within HDM extract. PTL11028 can completely inhibit Der p 1-mediated CD23 cleavage from human B cells and also reduces HDM-induced human bronchial epithelial cell permeability by 50%. Der p 1 is potently inhibited by cystatin A and to a lesser extent by cystatins C and E/M. Conclusion PTL11028 is a highly potent and selective irreversible inhibitor of the cysteine protease activity of Der p 1, an activity that may be modulated in vivo by some human cystatins. PTL11028 prevents the Der p 1-mediated cleavage of CD23 from human B cells and significantly reduces HDM-induced permeabilization of the epithelial barrier. PTL11028 is an important tool to examine the biological effects of Der p 1 in a range of in vitro and in vivo model systems.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 09:43:34