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One or more keywords matched the following properties of Boyce, Joshua
overview The overall goal of my lab is to apply principals of pathophysiology of allergic diseases in humans to questions at the bench, and in turn to bring fundamental findings made at the bench back to the clinic. The dominant themes include how lipid mediators and their receptors function in a network to control the development and activation of mast cells, a central cell type in the effector phases of all allergic diseases. We defined the growth factor requirements for the development of human mast cells from their earliest progenitors, and identified a key role for interleukin (IL)-4 as an accessory mitogen. Human mast cells exposed to IL-4 become competent to generate leukotriene C4 (LTC4) the precursor of the powerful bronchoconstrictor LTD4 and the stable metabolite LTE4. This competence is due to the induced expression of LTC4 synthase, the requisite terminal enzyme involved in LTC4 synthesis. These observations explain why mucosal inflammation elicits a mast cell hyperplasia accompanied by strikingly increased regional concentrations of LTC4 LTD4 and LTE4. We discovered that the growth potentiating effect of IL-4 depended on the induction of LTC4S, and the transactivation of the c-kit tyrosine kinase by the type 1 receptor for cys-LTs (CysLT1R). We also demonstrated that CysLT1R on mast cells exists as a heterodimer with the type 2 receptor for cys-LTs (CysLT2R), and that the latter is a potent negative regulator of the former. Most recently, we discovered that LTE4 only a weak agonist of CysLT1R and CysLT2R, is the most potent member of this mediator class for causing chemokine generation by mast cells and potentiating pulmonary inflammation in mice. These actions are due to the purinergic receptor P2Y12, which we have shown to be the long-elusive third cys-LT receptor. We plan to translate these observations into the clinic, and will test the efficacy of a P2Y12 antagonist on clinical reactions to aspirin challenge in aspirin-intolerant asthmatic individuals as a major goal of a U19 funded by NIAID.
One or more keywords matched the following items that are connected to Boyce, Joshua
Item TypeName
Academic Article Leukotriene E4 activates peroxisome proliferator-activated receptor gamma and induces prostaglandin D2 generation by human mast cells.
Academic Article Cysteinyl leukotriene receptor 1 is also a pyrimidinergic receptor and is expressed by human mast cells.
Academic Article Cysteinyl leukotrienes and their receptors: cellular distribution and function in immune and inflammatory responses.
Academic Article Coordinated involvement of mast cells and T cells in allergic mucosal inflammation: critical role of the CC chemokine ligand 1:CCR8 axis.
Academic Article Prostaglandin E2 deficiency uncovers a dominant role for thromboxane A2 in house dust mite-induced allergic pulmonary inflammation.
Academic Article Group V secretory phospholipase A2 reveals its role in house dust mite-induced allergic pulmonary inflammation by regulation of dendritic cell function.
Academic Article Cysteinyl leukotriene receptors, old and new; implications for asthma.
Academic Article The purinergic G protein-coupled receptor 6 inhibits effector T cell activation in allergic pulmonary inflammation.
Academic Article Fas-activated serine/threonine phosphoprotein promotes immune-mediated pulmonary inflammation.
Academic Article The translational repressor T-cell intracellular antigen-1 (TIA-1) is a key modulator of Th2 and Th17 responses driving pulmonary inflammation induced by exposure to house dust mite.
Academic Article Alpha-4 integrins and VCAM-1, but not MAdCAM-1, are essential for recruitment of mast cell progenitors to the inflamed lung.
Academic Article Prostaglandin E(2) exerts homeostatic regulation of pulmonary vascular remodeling in allergic airway inflammation.
Academic Article Eicosanoids in asthma, allergic inflammation, and host defense.
Academic Article The pathobiology of eosinophilic inflammation.
Academic Article Leukotriene E4-induced pulmonary inflammation is mediated by the P2Y12 receptor.
Academic Article Advances in mechanisms of asthma, allergy, and immunology in 2008.
Concept Inflammation Mediators
Concept Inflammation
Academic Article Group V secretory phospholipase A2 is involved in macrophage activation and is sufficient for macrophage effector functions in allergic pulmonary inflammation.
Academic Article Pathogenesis of aspirin-exacerbated respiratory disease and reactions.
Academic Article Impact of botanical oils on polyunsaturated fatty acid metabolism and leukotriene generation in mild asthmatics.
Academic Article Platelet-driven leukotriene C4-mediated airway inflammation in mice is aspirin-sensitive and depends on T prostanoid receptors.
Academic Article Leukotriene D4 and prostaglandin E2 signals synergize and potentiate vascular inflammation in a mast cell-dependent manner through cysteinyl leukotriene receptor 1 and E-prostanoid receptor 3.
Grant CysLT and P2Y Receptors in Lung Inflammation
Grant Chemical Mediators of Acute Pulmonary Disorders
Grant CysLt and P2Y Receptors and Lung Inflammation
Grant Cellular Basis of Hypersensitivity Diseases in Humans
Grant Eicosanoid Networks in Aspirin Exacerbated Respiratory Disease
Grant Regulation of Pulmonary Inflammation by Leukotriene E4
Grant CysLT and P2Y Receptors in Lung Inflammation
Grant Lipidomic and Transcriptome Signatures in Aspirin-Exacerbated Respiratory Disease
Grant The Role of Mast Cells in Lung Inflammation
Grant Pathophysiologic and Therapeutic Mechanisms in Aspirin Exacerbated Respiratory Disease
Grant Optimizing EP receptor subtype targeting for asthma therapy
Grant Eicosanoid Networks in Aspirin Hypersensitivity
Academic Article P2Y6 signaling in alveolar macrophages prevents leukotriene-dependent type 2 allergic lung inflammation.
Academic Article Lineage-specific regulation of inducible and constitutive mast cells in allergic airway inflammation.
Academic Article Human airway mast cells proliferate and acquire distinct inflammation-driven phenotypes during type 2 inflammation.
Search Criteria
  • Inflammation
Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.