COX Inhibition Increases Alternaria-Induced Pulmonary Group 2 Innate Lymphoid Cell Responses and IL-33 Release in Mice.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Weisong ZhouR Stokes Peebles

Abstract

The cyclooxygenase (COX) metabolic pathway regulates immune responses and inflammation. The effect of the COX pathway on innate pulmonary inflammation induced by protease-containing fungal allergens, such as Alternaria alternata, is not fully defined. In this study, we tested the hypothesis that COX inhibition augments Alternaria-induced pulmonary group 2 innate lymphoid cell (ILC2) responses and IL-33 release. Mice were treated with the COX inhibitors indomethacin, flurbiprofen, or vehicle and challenged intranasally with Alternaria extract for four consecutive days to induce innate lung inflammation. We found that indomethacin and flurbiprofen significantly increased the numbers of ILC2 and IL-5 and IL-13 expression by ILC2 in the lung. Indomethacin also increased ILC2 proliferation, the percentages of eosinophils, and mucus production in the lung. Both indomethacin and flurbiprofen augmented the release of IL-33 in bronchoalveolar lavage fluid after Alternaria challenge, suggesting that more IL-33 was available for ILC2 activation and that a COX product(s) inhibited IL-33 release. This is supported by the in vitro finding that the COX product PGE2 and the PGI2 analogs cicaprost decreased Alternaria extract-induced IL-33 rele...Continue Reading

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Citations

Sep 21, 2020·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·Kellen J Cavagnero, Taylor A Doherty
May 10, 2021·The Journal of Allergy and Clinical Immunology·Kathleen R Bartemes, Hirohito Kita
Aug 28, 2021·International Journal of Molecular Sciences·Geunyeong KimIn-Sik Kim
Sep 8, 2021·Experimental & Molecular Medicine·Sherry Sin-Hang YeungRaymond Chuen-Chung Chang
Sep 1, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Min Hwa HongIn Sik Kim

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