Atractylenolide III alleviates the apoptosis through inhibition of autophagy by the mTOR-dependent pathway in alveolar m
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Atractylenolide III alleviates the apoptosis through inhibition of autophagy by the mTOR‑dependent pathway in alveolar macrophages of human silicosis Shi Chen1 · Kun Tang2 · Peiwu Hu2 · Shiyi Tan1 · Shang Yang1 · Chang Yang1 · Gang Chen3 · Yixiao Luo1 · Hui Zou1 Received: 13 June 2020 / Accepted: 10 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Silica-induced apoptosis of alveolar macrophages (AMs) is an essential part of silicosis formation. Autophagy tends to present a bidirectional effect on apoptosis. Our previous study found that the blockade of autophagy degradation might aggravate the apoptosis of AMs in human silicosis. We presume that targeting the autophagic pathway is regarded as a promising new strategy for silicosis fibrosis. As a main active component of the Atractylodes rhizome, Atractylenolide III (ATL-III) has been widely applied in clinical anti-inflammation. However, the effect and mechanism of ATL-III on autophagy in AMs of silicosis are unknown. In this study, we found that ATL-III might inhibit autophagy by mTOR-dependent manner, thereby improving the blockage of autophagic degradation in AMs. ATL-III alleviated the apoptosis of AMs in human silicosis. Furthermore, Rapamycin reversed the protective effect of ATL-III in AMs. These results indicate that ATL-III may be a potentially protective ingredient targeting autophagy for workers exposed to silica dust. These findings also suggest that inhibition of autophagy may be an effective way to alleviate the apoptosis of AMs in silicosis. Keywords Atractylenolide III · mTOR-dependent autophagy · Apoptosis · Alveolar macrophages · Silicosis Abbreviations ATL-III Atractylenolide III AMs Alveolar macrophages Akt Protein kinase B DAPI 4′,6-Diamidino-2-phenylindole Electronic supplementary material The online version of this article (doi:https://doi.org/10.1007/s11010-020-03946-w) contains supplementary material, which is available to authorized users. * Yixiao Luo [email protected] * Hui Zou [email protected] 1
Key Laboratory of Molecular Epidemiology of Hunan Province, Hunan Normal University, NO. 371 Tongzipo Road, Changsha 410013, Hunan Province, People’s Republic of China
2
Xiangya Hospital, Central South University, Changsha 410005, Hunan Province, People’s Republic of China
3
Department of Pneumoconiosis, Beidaihe Sanitarium for China Coal Miners, Qinhuangdao 066104, Hebei Province, People’s Republic of China
DMEM Dulbecco modified Eagle medium FBS Fetal bovine serum LAMP2 Lysosomal associated membrane protein 2 LC3 Microtubule-associated protein 1 light chain 3 mTOR Mammalian target of rapamycin PI3K Phosphatidylinositol 3-kinase p62 Sequestosome 1 Rap Rapamycin Ser Serine Thr Threomine
Introduction Silicosis, the most common and severe type of pneumoconiosis, is caused by the inhalation of free silica dust continuously [1]. Silica-induced apoptosis of alveolar macrophages (AMs) is a vital part of silicosis development. Apoptotic AMs, coupled with engulfed silica
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