The Phosphodiesterase 4 Inhibitor Roflumilast Protects against Cigarette Smoke Extract-Induced Mitophagy-Dependent Cell Death in Epithelial Cells

Kyung, Sun Young; Kim, Yu Jin; Son, Eun Suk; Jeong, Sung Hwan; Park, Jeong-Woong

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자료유형: 학술저널

저자정보: Kyung, Sun Young (Division of Pulmonary, Department of Internal Medicine, Gachon University Gil Medical Center) Kim, Yu Jin (Division of Pulmonary, Department of Internal Medicine, Gachon University Gil Medical Center) Son, Eun Suk (Division of Pulmonary, Department of Internal Medicine, Gachon University Gil Medical Center) Jeong, Sung Hwan (Division of Pulmonary, Department of Internal Medicine, Gachon University Gil Medical Center) Park, Jeong-Woong (Division of Pulmonary, Department of Internal Medicine, Gachon University Gil Medical Center)

저널정보: 대한결핵 및 호흡기학회 Tuberculosis and Respiratory Diseases 결핵 및 호흡기 질환 제81권 제2호

발행연도: 2018.1

수록면: 138 - 147 (10page)

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Background: Recent studies show that mitophagy, the autophagy-dependent turnover of mitochondria, mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure and contributes to the development of emphysema in vivo during chronic cigarette smoke (CS) exposure, although the underlying mechanisms remain unclear. Methods: In this study, we investigated the role of mitophagy in the regulation of CSE-exposed lung bronchial epithelial cell (Beas-2B) death. We also investigated the role of a phosphodiesterase 4 inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death. Results: Our results demonstrated that CSE induces mitophagy in Beas-2B cells through mitochondrial dysfunction and increased the expression levels of the mitophagy regulator protein, PTEN-induced putative kinase-1 (PINK1), and the mitochondrial fission protein, dynamin-1-like protein (DRP1). CSE-induced epithelial cell death was significantly increased in Beas-2B cells exposed to CSE but was decreased by small interfering RNA-dependent knockdown of DRP1. Treatment with roflumilast in Beas-2B cells inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting the expression of phospho-DRP1 and -PINK1. Roflumilast protected against cell death and increased cell viability, as determined by the lactate dehydrogenase release test and the MTT assay, respectively, in Beas-2B cells exposed to CSE. Conclusion: These findings suggest that roflumilast plays a protective role in CS-induced mitophagy-dependent cell death.

#Mitophagy #Roflumilast #Tobacco Use #Pulmonary Disease #Chronic Obstructive

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