Accentuated T helper type 2 airway response after allergen challenge in cyclooxygenase-1-/- but not cyclooxygenase-2-/- mice.
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.
Carey
Michelle A
MA
National Institute of Environmental Health Sciences/NIH, 111 TW Alexander Drive, Building 101, Research Triangle Park, NC 27709, USA.
Germolec
Dori R
DR
Bradbury
J Alyce
JA
Gooch
Rebecca A
RA
Moorman
Michael P
MP
Flake
Gordon P
GP
Langenbach
Robert
R
Zeldin
Darryl C
DC
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*
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