Allergen-Induced Airway Hyperresponsiveness Mediated by Cyclooxygenase Inhibition Is Not Dependent on 5-Lipoxygenase or IL-5, but Is IL-13 Dependent

Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
The Journal of Immunology (Impact Factor: 4.92). 02/2006; 175(12):8253-9. DOI: 10.1016/j.jaci.2005.12.580
Source: PubMed


Cyclooxygenase (COX) inhibition during allergic sensitization and allergen airway challenge results in augmented allergic inflammation. We hypothesized that this increase in allergic inflammation was dependent on increased generation of leukotrienes that results from COX inhibition, as leukotrienes are important proinflammatory mediators of allergic disease. To test this hypothesis, we allergically sensitized and challenged mice deficient in 5-lipoxygenase (5-LO). We found that 5-LO knockout mice that were treated with a COX inhibitor during allergic sensitization and challenge had significantly increased airway hyperresponsiveness (AHR) (p < 0.01) and airway eosinophilia (p < 0.01) compared with 5-LO knockout mice that were treated with vehicle. The proinflammatory cytokines have also been hypothesized to be critical regulators of airway inflammation and AHR. We found that the increase in airway eosinophilia seen with COX inhibition is dependent on IL-5, whereas the increase in AHR is not dependent on this cytokine. In contrast, the COX inhibition-mediated increase in AHR is dependent on IL-13, but airway eosinophilia is not. These results elucidate the pathways by which COX inhibition exerts a critical effect of the pulmonary allergen-induced inflammatory response and confirm that COX products are important regulators of allergic inflammation.

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Available from: Koichi Hashimoto, Oct 13, 2015
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    • "In this study we showed that OVA allergic mice exhibited high levels of specific serum anti-OVA IgE and IgG1, a response suppressed under conditions of FO administration. The augmentation of serum levels of IgE and IgG1 under conditions of allergen sensitization has been shown previously [40–42]. Our data are in line with previous report showing that IgE production was reduced by FO in primary human B cells in vitro [10] and that both IgE and IgG1 were diminished after FO administration to OVA-sensitized mice [43]. "
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    PLoS ONE 09/2013; 8(9):e75059. DOI:10.1371/journal.pone.0075059 · 3.23 Impact Factor
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    • "The resulting reduced production of endogenous PGE2 and mPGE synthase may be directly linked to the observed worsening of AHR according to previous observations [13]. Using an alternative experimental approach, Peebles et al. [26] showed an IL-13-dependent increased AHR under COX-2 inhibition in OVA-sensitized mice. We presume that this Th2 cytokine might at least partly explain our increased AHR [29], but other elements, such as cys-leukotrienes, which presumably are increased when the COX pathway is partly blocked, should not be ruled out as directly responsible for the in vivo worsening of airway function in the presence of antisense oligonucleotide targeting COX-2 [47,48]. "
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