Author/Authors :
Lee, Jong-Uk Department of Interdisciplinary Program in Biomedical Science Major - Soonchunhyang Graduate School, Bucheon, Republic of Korea , Sook Park, Jong Division of Allergy and Respiratory Medicine - Department of Internal Medicine - Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea , Jun, Ji Ae Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea , Kyung Kim, Min Department of Interdisciplinary Program in Biomedical Science Major - Soonchunhyang Graduate School, Bucheon, Republic of Korea , Chang, Hun Soo Department of Interdisciplinary Program in Biomedical Science Major - Soonchunhyang Graduate School, Bucheon, Republic of Korea , Gyu Baek, Dong Department of Interdisciplinary Program in Biomedical Science Major - Soonchunhyang Graduate School, Bucheon, Republic of Korea , Ji Song, Hyun Department of Interdisciplinary Program in Biomedical Science Major - Soonchunhyang Graduate School, Bucheon, Republic of Korea , Kim, Myung-Sin Department of Internal Medicine - Soonchunhyang University Gumi Hospital, Gumi, Gyeongsangbuk-do, Republic of Korea , Park, Choon-Sik Division of Allergy and Respiratory Medicine - Department of Internal Medicine - Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea
Abstract :
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. ,e 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-c, 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-c levels were markedly attenuated. Conclusion. ,ese data indicate that
paquinimod effectively inhibits neutrophilic inflammation and remodeling in the murine model of neutrophilic asthma, possibly via
downregulation of IL-17, IFN-c, and IL-1β
