Mefloquine improves pulmonary fibrosis by inhibiting the KCNH2/Jak2/Stat3 signaling pathway in macrophages

Jiawei Zhou; Xuelian Yang; Yafeng Liu; Jianqiang Guo; Ziqin Liu; Yunyun Li; Ying Bai; Yingru Xing; Jing Wu; Dong Hu

Biomedicine & Pharmacotherapy (Feb 2024)

Mefloquine improves pulmonary fibrosis by inhibiting the KCNH2/Jak2/Stat3 signaling pathway in macrophages

Jiawei Zhou,
Xuelian Yang,
Yafeng Liu,
Jianqiang Guo,
Ziqin Liu,
Yunyun Li,
Ying Bai,
Yingru Xing,
Jing Wu,
Dong Hu

Affiliations

Jiawei Zhou: School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, China
Xuelian Yang: School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China
Yafeng Liu: School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, China
Jianqiang Guo: School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, China
Ziqin Liu: School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, China
Yunyun Li: School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, China
Ying Bai: School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, China; Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Huainan, Anhui, China
Yingru Xing: Department of Clinical Laboratory, Anhui Zhongke Gengjiu Hospital, Hefei, China
Jing Wu: School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, China; Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Huainan, Anhui, China; Key Laboratory of Industrial Dust Prevention and Control & Occupational Safety and Health of the Ministry of Education, Anhui University of Science and Technology, Huainan, Anhui, China; Corresponding authors at: School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China.
Dong Hu: School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China; Anhui Occupational Health and Safety Engineering Laboratory, Huainan, Anhui, China; Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Huainan, Anhui, China; Key Laboratory of Industrial Dust Prevention and Control & Occupational Safety and Health of the Ministry of Education, Anhui University of Science and Technology, Huainan, Anhui, China; Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, China; Corresponding authors at: School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China.

Journal volume & issue: Vol. 171
p. 116138

Abstract

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Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease characterized by severe pulmonary fibrosis, for which there is an urgent need for effective therapeutic agents. Mefloquine (Mef) is a quinoline compound primarily used for the treatment of malaria. However, high doses (>25 mg/kg) may lead to side effects such as cardiotoxicity and psychiatric disorders. Here, we found that low-dose Mef (5 mg/kg) can safely and effectively treat IPF mice. Functionally, Mef can improve the pulmonary function of IPF mice (PIF, PEF, EF50, VT, MV, PENH), alleviating pulmonary inflammation and fibrosis by inhibiting macrophage activity. Mechanically, Mef probably regulates the Jak2/Stat3 signaling pathway by binding to the 492HIS site of Potassium voltage-gated channel subfamily H member 2 (KCNH2) protein in macrophages, inhibiting the secretion of macrophage inflammatory and fibrotic factors. In summary, Mef may inhibit macrophage activity by binding to KCNH2 protein, thereby slowing down the progress of IPF.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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