Atractylenolide III alleviates the apoptosis through inhibition of autophagy by the mTOR-dependent pathway in alveolar macrophages of human silicosis

Mol Cell Biochem. 2021 Feb;476(2):809-818. doi: 10.1007/s11010-020-03946-w. Epub 2020 Oct 19.

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: Alveolar macrophages; Apoptosis; Atractylenolide III; Silicosis; mTOR-dependent autophagy.

MeSH terms

  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Bronchoalveolar Lavage Fluid / cytology*
  • Cells, Cultured
  • Cholinergic Antagonists / pharmacology
  • Humans
  • Lactones / pharmacology*
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / pathology
  • Sesquiterpenes / pharmacology*
  • Silicosis / drug therapy*
  • Silicosis / metabolism
  • Silicosis / pathology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Cholinergic Antagonists
  • Lactones
  • Sesquiterpenes
  • atractylenolide III
  • MTOR protein, human
  • TOR Serine-Threonine Kinases