Aspirin-Exacerbated Respiratory Disease Involves a Cysteinyl Leukotriene-Driven IL-33-Mediated Mast Cell Activation Pathway.

ABSTRACT: Aspirin-exacerbated respiratory disease (AERD), a severe eosinophilic inflammatory disorder of the airways, involves overproduction of cysteinyl leukotrienes (cysLTs), activation of airway mast cells (MCs), and bronchoconstriction in response to nonselective cyclooxygenase inhibitors that deplete homeostatic PGE2. The mechanistic basis for MC activation in this disorder is unknown. We now demonstrate that patients with AERD have markedly increased epithelial expression of the alarmin-like cytokine IL-33 in nasal polyps, as compared with polyps from aspirin-tolerant control subjects. The murine model of AERD, generated by dust mite priming of mice lacking microsomal PGE2 synthase (ptges(-/-) mice), shows a similar upregulation of IL-33 protein in the airway epithelium, along with marked eos

SUBMITTER: Liu T 

PROVIDER: S-EPMC4592820 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature