Prostaglandin E2prevents mast cell dependent bronchoconstrictrionviathe EP2receptor in human small airways

Le résumé fourni par la source

The hypothesis that PGE2 prevents allergic bronchoconstriction via EP2 receptors on mast cells in human bronchi was tested. Small bronchi (inner diameter of 0.5-1 mm) were isolated from macroscopically healthy human lung tissue obtained from 56 patients undergoing surgery. Mast cell-dependent contractions were produced by challenge with an anti-human IgE antibody (anti-IgE;51.8 μg/ml). The mast cell mediators histamine and cysteinyl-leukotrienes (CysLTs) were measured. Pre-treatment with PGE2 concentration-dependently (0.1-10µM) reduced the anti-IgE induced contraction (Figure 1A, blue;p<0.05). The inhibitory effect of PGE2 10 µM was completely antagonised by the EP2 receptor antagonist PF-04418948 (Figure 1A, red;p<0.05), but unaffected by the EP4 antagonist ONO-AE3-208 (Figure 1A, green). PGE2 100 nM also inhibited the anti-IgE-induced release of histamine and CysLTs (Figure 1B-C; p<0.05). This protective effect of PGE2 on mediator release was completely reversed by pre-treatment with the EP2 receptor antagonist PF-04418948 (Figure 1B-C; p<0.05). This first demonstration of EP2 receptor mediated inhibition of IgE-dependent contractions of isolated small human airways introduces a new selective target for treatment of asthma. Figure 1: Anti-IgE after PGE2 treatment (A) in presence of EP2 (PF044) or EP4 (ONO208) receptor antagonists and corresponding media measurement of (B) histamine and (C) CysLT (n:5-9).

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.