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The Antidiabetic Agent Glibenclamide Protects Airway Hyperresponsiveness and Inflammation in Mice

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Abstract

Glibenclamide has a newly discovered role in inflammation regulation besides its antidiabetic effect. As an inhibitor of ATP-sensitive potassium (KATP) channel, glibenclamide antagonizes the relaxation of the tracheal smooth muscle. This indicates that glibenclamide might attenuate airway inflammation while aggravate airway hyperresponsiveness (AHR) in asthmatics. Clinically, many diabetics with asthma are prescribed with glibenclamide to control blood glucose. However, whether glibenclamide could exert any effects on asthmatic inflammation remains unknown. Using an ovalbumin (OVA)-induced mouse model of asthma, we evaluated the effects of glibenclamide on the AHR and inflammation. Interestingly, glibenclamide reduced all the cardinal features of asthma in OVA-challenged mice, including AHR, airway inflammation, and T-helper type 2 (Th2) cytokines. Glibenclamide also downregulated OVA-induced expressions of vascular cell adhesion molecule 1 (VCAM-1) and phosphorylated signal transducer and activator of transcription 6 (p-STAT6) in the lung. In addition, increased sulfonylurea receptor 1 (SUR1) expression in the lung was observed after the OVA challenge. These findings suggest that the classic sulfonylurea glibenclamide plays an important protective role in the development of asthma, which not only provides the evidence for the safety of prescribed glibenclamide in diabetics combined with asthma but also indicates a possible new therapeutic for asthma via targeting glibenclamide-related pathways.

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Acknowledgments

This study was supported, in part, by the grants from the Natural Science Foundation of Zhejiang Province, China (No. Y2110062, Cui W), the General Medical and Health Research Program (No. 2013KYA085, GS Zhang), the Qianjiang Talent Program (No. 2013R10050, GS Zhang) of Zhejiang Province, Research Fund for the Doctoral Program of Higher Education of China (No. 20130101120035, GS Zhang), and the National Natural Science Foundation of China (No. 81300015, GS Zhang).

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The authors have declared no conflict of interest in the publication of this manuscript.

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Correspondence to Gensheng Zhang.

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Authors’ Contributions

Wei Cui and Shufang Zhang contributed to the design of the experiments, acquisition and analysis of the data, and the initial draft writing of this manuscript. Zhijian Cai, Xinlei Hu, Ruifeng Zhang, Yong Wang, Na Li, and Zhihua Chen contributed to the collection and analysis and interpretation of data. Gensheng Zhang contributed to the conception and design of the experiments, was involved in the interpretation of experimental results, revised this manuscript, and contributed to the final approval of the version to be published.

Wei Cui and Shufang Zhang contributed equally to this work.

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Cui, W., Zhang, S., Cai, Z. et al. The Antidiabetic Agent Glibenclamide Protects Airway Hyperresponsiveness and Inflammation in Mice. Inflammation 38, 835–845 (2015). https://doi.org/10.1007/s10753-014-9993-z

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