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Glyburide attenuates ozone‐induced pulmonary inflammation and injury by blocking the NLRP3 inflammasome
Author(s) -
Shao Hua,
Huang Li,
Duan Shuyin,
Gao Min,
Zhu Jiacheng,
Chen Xiaohui,
Zhu Yajuan,
Wang Wenhan,
Yang Zengwen,
Wang Xinyu,
Wang Zhen,
Wang Zhimin,
Ba Yue,
Zhang Ruiqin,
Li Chunyang,
Zhang Qiao,
Wang Jing,
Liu Hong,
Wu Weidong,
Feng Feifei
Publication year - 2020
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22919
Subject(s) - inflammasome , bronchoalveolar lavage , inflammation , lung , caspase 1 , chemistry , blot , interleukin , immunology , pharmacology , medicine , cytokine , biochemistry , gene
Glyburide is a classic antidiabetic drug that is dominant in inflammation regulation, but its specific role in ozone‐induced lung inflammation and injury remains unclear. In order to investigate whether glyburide prevents ozone‐induced pulmonary inflammation and its mechanism, C57BL/6 mice were intratracheally pre‐instilled with glyburide or the vehicle 1 hour before ozone (1 ppm, 3 hours) or filtered air exposure. After 24 hours, the total inflammatory cells and total protein in bronchoalveolar lavage fluid (BALF) were detected. The pathological alternations in lung tissues were evaluated by HE staining. The expression of NLRP3, interleukin‐1β (IL‐1β), and IL‐18 protein in lung tissues was detected by immunohistochemistry. Western blotting was used to examine the levels of caspase‐1 p10 and active IL‐1β protein. Levels of IL‐1β and IL‐18 in BALF were measured using ELISA kits. Glyburide treatment decreased the total cells in BALF, the inflammatory score, and the mean linear intercept induced by ozone in lung tissues. In addition, glyburide inhibited the expression of NLRP3, IL‐18, and IL‐1β protein in lung tissues, and also suppressed NLRP3 inflammasome activation, including caspase‐1 p10, active IL‐1β protein in lung tissues, IL‐1β, and IL‐18 in BALF. These results demonstrate that glyburide effectively attenuates ozone‐induced pulmonary inflammation and injury via blocking the NLRP3 inflammasome.

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