Journal article
G(s)-Coupled Adenosine Receptors Differentially Limit Antigen-Induced Mast Cell Activation
The Journal of pharmacology and experimental therapeutics, Vol.344(2), pp.426-435
02/01/2013
DOI: 10.1124/jpet.112.198978
PMCID: PMC3558828
PMID: 23149337
Abstract
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 A(2B) receptors, suggest that adenosine receptors, specifically the G(s)-coupled A(2A) and A(2B) 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 A(2B) as the primary receptor limiting mast cell degranulation, whereas the combined activity of A(2A) and A(2B) is required for the inhibition of cytokine synthesis.
Details
- Title: Subtitle
- G(s)-Coupled Adenosine Receptors Differentially Limit Antigen-Induced Mast Cell Activation
- Creators
- Xiaoyang Hua - University of North Carolina at Chapel HillKelly D. Chason - University of North Carolina at Chapel HillCorey Jania - University of North Carolina at Chapel HillTatiana Acosta - University of North Carolina at Chapel HillCatherine Ledent - Université Libre de BruxellesStephen L. Tilley - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.344(2), pp.426-435
- Publisher
- Amer Soc Pharmacology Experimental Therapeutics
- DOI
- 10.1124/jpet.112.198978
- PMID
- 23149337
- PMCID
- PMC3558828
- ISSN
- 0022-3565
- eISSN
- 1521-0103
- Number of pages
- 10
- Grant note
- R01HL071802 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R20926 / North Carolina Translational and Clinical Sciences Institute 92997 / American Academy of Otolaryngology-Head and Neck Surgery/American Academy of Otolaryngic Allergy HL071802; AI096139 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R21AI096139 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Language
- English
- Date published
- 02/01/2013
- Academic Unit
- Otolaryngology
- Record Identifier
- 9984312247002771
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