Background: Prostaglandin (PG) E2 is thought to exert protective effects in the lungs. Accordingly, aerosolized PGE2 prevents the experimentally induced airway response to allergen challenge in asthmatics. In vitro evidence indicating that functional PGE2 receptors (EP) are expressed on human mast cells and that PGE2 can alter cytokine production suggests that these phenomena may be involved in its beneficial effect in asthma. However, in vivo evidence is scarce. Methods: We assessed the effects of exogenous PGE2 and of the EP1/EP3 agonist sulprostone on the murine airway response to house dust mite (HDM) allergens, a model that accurately reproduces the spontaneous exposure of allergic asthma patients to aeroallergens. We also analyzed the in vivo impact of PGE2 on production in the murine airway of mast cell protease (mMCP)-1, a specific marker of lung mast cell activity, and on local production of cytokines. Results: Exogenous PGE2, but not sulprostone, reduced eosinophilic infiltration in HDM-sensitized mice by half and led to a strong reduction in airway Th2 cytokine expression. These anti- inflammatory effects were accompanied in vivo by a substantial reduction in HDM-induced upregulation of airway mMCP-1. Neither PGE2 nor sulprostone had any effect on airway hyperresponsiveness to methacholine. Conclusions: Our results indicate that the anti-inflammatory effect of PGE2 can be reproduced in vivo in HDM-sensitized mice and suggest that this protective effect is dependent in vivo on inhibition of the allergen-triggered proinflammatory activity of bronchial mast cells. Finally, the effect of PGE2 is linked to reduced upregulation of airway Th2 cytokines.

Keywords:
Allergic asthma, Cytokines, Mast cells, Prostaglandin E2
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2009
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