Inhibition of Both Cyclooxygenase-1 and -2 Promotes Epicutaneous Th2 and Th17 Sensitization and Allergic Airway Inflammation on Subsequent Airway Exposure to Protease Allergen in Mice

<b><i>Introduction:</i></b> Epicutaneous (e.c.) allergen exposure is an important route of sensitization toward allergic diseases in the atopic march. Allergen sources such as house dust mites contain proteases that involve pathogenesis allergy. Prostanoids produced via pathways downstream cyclooxygenases (COXs) regulate immune responses. Here, we demonstrate effects COX inhibition with nonsteroidal anti-inflammatory drugs (NSAIDs) on e.c. to protease and subsequent airway inflammation mice. <b><i>Methods:</i></b> Mice were treated NSAIDs during a model allergen, papain, and/or intranasal challenge low-dose papain. Serum antibodies, cytokine production antigen-restimulated skin or bronchial draining lymph node (DLN) cells, analyzed. <b><i>Results:</i></b> In sensitization, treatment nonspecific inhibitor, indomethacin, promoted serum total papain-specific IgE response Th2 Th17 DLN cells. After challenge, indomethacin which depended modestly largely respectively. Co-treatment COX-1-selective COX-2-selective inhibitors cell Th responses more efficiently than either selective inhibitor. <b><i>Conclusion:</i></b> The results suggest overall prostanoids are suppressive for development expansion not only but also, unexpectedly, upon allergens airways inflammation.