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Accentuated T Helper Type 2 Airway Response after Allergen Challenge in Cyclooxygenase-1^-/- but Not Cyclooxygenase-2^-/- Mice

Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina

Correspondence and requests for reprints should be addressed to Darryl C. Zeldin, National Institute of Environmental Health Sciences/NIH, 111 TW Alexander Drive, Building 101, Research Triangle Park, NC 27709. E-mail: zeldin{at}niehs.nih.gov

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.

Key Words: cyclooxygenase • Th2 cytokine • ovalbumin

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