Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund’s Adjuvant
Background. Quinoline-3-carboxamides have been used to treat autoimmune/inflammatory diseases in humans because they inhibit the functions of S100 calcium-binding protein A9 (S100A9), which participates in the development of neutrophilic inflammation in asthmatics and in an animal model of neutrophi...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Canadian Respiratory Journal |
| Online Access: | http://dx.doi.org/10.1155/2021/8896108 |
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| author | Jong-Uk Lee Jong Sook Park Ji Ae Jun Min Kyung Kim Hun Soo Chang Dong Gyu Baek Hyun Ji Song Myung-Sin Kim Choon-Sik Park |
| author_facet | Jong-Uk Lee Jong Sook Park Ji Ae Jun Min Kyung Kim Hun Soo Chang Dong Gyu Baek Hyun Ji Song Myung-Sin Kim Choon-Sik Park |
| author_sort | Jong-Uk Lee |
| collection | DOAJ |
| description | Background. Quinoline-3-carboxamides have been used to treat autoimmune/inflammatory diseases in humans because they inhibit the functions of S100 calcium-binding protein A9 (S100A9), which participates in the development of neutrophilic inflammation in asthmatics and in an animal model of neutrophilic asthma. However, the therapeutic effects of these chemicals have not been evaluated in asthma. The purpose of this study was to evaluate the effect of paquinimod, one of the quinoline-3-carboxamides, on a murine model of neutrophilic asthma. Methods. Paquinimod was orally administered to 6-week-old C57BL/6 mice sensitized and challenged with ovalbumin (OVA)/complete Freund’s adjuvant (CFA) and OVA. Lung inflammation and remodeling were evaluated using bronchoalveolar lavage (BAL) and histologic findings including goblet cell count. S100A9, caspase-1, IL-1β, MPO, IL-17, IFN-γ, and TNF-α were measured in lung lysates using western blotting. Results. Paquinimod restored the enhancement of airway resistance and the increases in numbers of neutrophils and macrophages of BAL fluids and those of goblet cells in OVA/CFA mice toward the levels of sham-treated mice in a dose-dependent manner (0.1, 1, 10, and 25 mg/kg/day, p.o.). Concomitantly, p20 activated caspase-1, IL-1β, IL-17, TNF-α, and IFN-γ levels were markedly attenuated. Conclusion. These data indicate that paquinimod effectively inhibits neutrophilic inflammation and remodeling in the murine model of neutrophilic asthma, possibly via downregulation of IL-17, IFN-γ, and IL-1β. |
| format | Article |
| id | doaj-art-e76c1205807344ed9aba05759afcb961 |
| institution | OA Journals |
| issn | 1198-2241 1916-7245 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Canadian Respiratory Journal |
| spelling | doaj-art-e76c1205807344ed9aba05759afcb9612025-08-20T02:21:09ZengWileyCanadian Respiratory Journal1198-22411916-72452021-01-01202110.1155/2021/88961088896108Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund’s AdjuvantJong-Uk Lee0Jong Sook Park1Ji Ae Jun2Min Kyung Kim3Hun Soo Chang4Dong Gyu Baek5Hyun Ji Song6Myung-Sin Kim7Choon-Sik Park8Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Republic of KoreaDivision of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of KoreaPulmoBioPark Co.,Ltd., Soonchunhyang University Bucheon Hospital, Bucheon, Republic of KoreaDepartment of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Republic of KoreaDepartment of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Republic of KoreaDepartment of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Republic of KoreaDepartment of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Republic of KoreaDepartment of Internal Medicine, Soonchunhyang University Gumi Hospital, Gumi, Gyeongsangbuk-do 39371, Republic of KoreaDivision of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of KoreaBackground. Quinoline-3-carboxamides have been used to treat autoimmune/inflammatory diseases in humans because they inhibit the functions of S100 calcium-binding protein A9 (S100A9), which participates in the development of neutrophilic inflammation in asthmatics and in an animal model of neutrophilic asthma. However, the therapeutic effects of these chemicals have not been evaluated in asthma. The purpose of this study was to evaluate the effect of paquinimod, one of the quinoline-3-carboxamides, on a murine model of neutrophilic asthma. Methods. Paquinimod was orally administered to 6-week-old C57BL/6 mice sensitized and challenged with ovalbumin (OVA)/complete Freund’s adjuvant (CFA) and OVA. Lung inflammation and remodeling were evaluated using bronchoalveolar lavage (BAL) and histologic findings including goblet cell count. S100A9, caspase-1, IL-1β, MPO, IL-17, IFN-γ, and TNF-α were measured in lung lysates using western blotting. Results. Paquinimod restored the enhancement of airway resistance and the increases in numbers of neutrophils and macrophages of BAL fluids and those of goblet cells in OVA/CFA mice toward the levels of sham-treated mice in a dose-dependent manner (0.1, 1, 10, and 25 mg/kg/day, p.o.). Concomitantly, p20 activated caspase-1, IL-1β, IL-17, TNF-α, and IFN-γ levels were markedly attenuated. Conclusion. These data indicate that paquinimod effectively inhibits neutrophilic inflammation and remodeling in the murine model of neutrophilic asthma, possibly via downregulation of IL-17, IFN-γ, and IL-1β.http://dx.doi.org/10.1155/2021/8896108 |
| spellingShingle | Jong-Uk Lee Jong Sook Park Ji Ae Jun Min Kyung Kim Hun Soo Chang Dong Gyu Baek Hyun Ji Song Myung-Sin Kim Choon-Sik Park Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund’s Adjuvant Canadian Respiratory Journal |
| title | Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund’s Adjuvant |
| title_full | Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund’s Adjuvant |
| title_fullStr | Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund’s Adjuvant |
| title_full_unstemmed | Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund’s Adjuvant |
| title_short | Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund’s Adjuvant |
| title_sort | inhibitory effect of paquinimod on a murine model of neutrophilic asthma induced by ovalbumin with complete freund s adjuvant |
| url | http://dx.doi.org/10.1155/2021/8896108 |
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