COX Inhibition Increases
| Autor: | Weisong, Zhou, Jian, Zhang, Shinji, Toki, Kasia, Goleniewska, Allison E, Norlander, Dawn C, Newcomb, Pingsheng, Wu, Kelli L, Boyd, Hirohito, Kita, R Stokes, Peebles |
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| Rok vydání: | 2020 |
| Předmět: |
Indomethacin
Alternariosis Article Mice otorhinolaryngologic diseases Animals Humans Cyclooxygenase Inhibitors Lymphocytes Lung Cell Proliferation Mice Knockout Mice Inbred BALB C Interleukin-13 Alternaria Epithelial Cells Pneumonia Allergens Interleukin-33 Immunity Innate Eosinophils Flurbiprofen lipids (amino acids peptides and proteins) Female Interleukin-5 Bronchoalveolar Lavage Fluid |
| Zdroj: | J Immunol |
| ISSN: | 1550-6606 |
| Popis: | 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 inhibitor 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 PGE(2) and the PGI(2) analogs cicaprost decreased Alternaria extract-induced IL-33 release by human bronchial epithelial cells. Although contrasting effects of PGD(2), PGE(2), and PGI(2) on ILC2 responses have been previously reported, the overall effect of the COX pathway on ILC2 function is inhibitory in Alternaria-induced innate airway inflammation. (Word count: Abstract 211; Manuscript: 5109) |
| Databáze: | OpenAIRE |
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