par Hua, Xiaoyang;Chason, Kelly K.D.;Jania, Corey;Acosta, Tatiana;Ledent, Catherine 
;Tilley, Stephen S.L.
Référence The Journal of pharmacology and experimental therapeutics, 344, 2, page (426-435)
Publication Publié, 2013-02
;Tilley, Stephen S.L.Référence The Journal of pharmacology and experimental therapeutics, 344, 2, page (426-435)
Publication Publié, 2013-02
Article révisé par les pairs
| Résumé : | Mast cell activation results in the immediate release of proinflammatory mediators prestored in cytoplasmic granules, as well as initiation of lipid mediator production and cytokine synthesis by these resident tissue leukocytes. Allergen-induced mast cell activation is central to the pathogenesis of asthma and other allergic diseases. Presently, most pharmacological agents for the treatment of allergic disease target receptors for inflammatory mediators. Many of these mediators, such as histamine, are released by mast cells. Targeting pathways that limit antigen-induced mast cell activation may have greater therapeutic efficacy by inhibiting the synthesis and release of many proinflammatory mediators produced in the mast cell. In vitro studies using cultured human and mouse mast cells, and studies of mice lacking A2B receptors, suggest that adenosine receptors, specifically the G s-coupled A2A and A2B receptors, might provide such a target. Here, using a panel of mice lacking various combinations of adenosine receptors, and mast cells derived from these animals, we show that adenosine receptor agonists provide an effective means of inhibition of mast cell degranulation and induction of cytokine production both in vitro and in vivo. We identify A2B as the primary receptor limiting mast cell degranulation, whereas the combined activity of A2A and A 2B is required for the inhibition of cytokine synthesis. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics. |
