title: Accentuated T helper type 2 airway response after allergen challenge in cyclooxygenase-1-/- but not cyclooxygenase-2-/- mice.
abstract: Acute pharmacologic inhibition of cyclooxygenase (COX)-1 or -2 during allergen sensitization and exposure leads to enhanced T helper type 2 (Th2) airway responses. COX-1 and -2 play functionally distinct roles in lymphocyte development, and consequently, genetic deficiency of either enzyme, as opposed to acute pharmacologic inhibition, may modulate Th2-mediated allergic airway disease differently. An ovalbumin-induced mouse model of allergic airway disease was used. The immunophenotype of bronchoalveolar lavage lymphocytes was assessed by flow cytometry, bronchoalveolar lavage cytokines, and chemokines were measured by enzyme-linked immunosorbent assay, adhesion molecule expression was assessed by immunoblotting in combination with immunohistochemistry, and bronchoconstriction was assessed by whole body plethysmography. The airways of COX-1-/- mice contained increased numbers of CD4+ and CD8+ T cells, exaggerated levels of the Th2 cytokines interleukin-4, -5, and -13, and increased levels of eotaxin and thymus- and activation-regulated chemokine. Allergen-induced bronchoconstriction was also increased in COX-1-/- mice. Vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 levels were increased in lungs of both COX-1-/- and COX-2-/- mice relative to wild type. These data suggest that genetic deficiency of COX-1 but not COX-2 modulates T cell recruitment, Th2 cytokine secretion, and lung function in the allergic airway.
authors.affiliation: National Institute of Environmental Health Sciences/NIH, 111 TW Alexander Drive, Building 101, Research Triangle Park, NC 27709, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Carey
authors.forename: Dori R
authors.initials: DR
authors.lastname: Germolec
authors.forename: J Alyce
authors.initials: JA
authors.lastname: Bradbury
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Gooch
authors.forename: Michael P
authors.initials: MP
authors.lastname: Moorman
authors.forename: Gordon P
authors.initials: GP
authors.lastname: Flake
authors.forename: Robert
authors.initials: R
authors.lastname: Langenbach
authors.forename: Darryl C
authors.initials: DC
authors.lastname: Zeldin
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000276:immunology*; D018925:Chemokines / Q000276:immunology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000276:immunology; D005260:Female; D015151:Immunoblotting; D016130:Immunophenotyping; D007527:Isoenzymes / Q000172:deficiency / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D018925:Chemokines; D016207:Cytokines; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse