Particulate matter 2.5 induced bronchial epithelial cell injury via activation of 5′‐adenosine monophosphate‐activated protein kinase‐mediated autophagy

Abstract

The impact of particulate matter 2.5 (PM2.5) on the respiratory system is a worldwide concern. However, the mechanisms by which PM2.5 causes disease are still unclear. In this study, we investigated the effect of PM2.5 on autophagy and studied the effect of PM2.5-induced autophagy and 5'-adenosine monophosphate-activated protein kinase (AMPK) on cell proliferation, cell cycle, apoptosis, reactive oxygen species (ROS), and airway inflammation using human bronchial epithelial cells 16HBE140 cells. Results showed that exposure of cells to PM2.5 at a concentration of 100 μg/mL for 24 hours was most effective for inhibiting cell viability. PM2.5 induced cell arrest in the G0/G1 phase and increased mitochondrial membrane potential, ROS, and cell apoptosis with increasing concentration. PM2.5 downregulated cyclin D and matrix metallopeptidase-9 (MMP-9) expression but upregulated tissue inhibitor of metalloproteinases-1 (TIMP-1) expression, significantly promoted interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) production, and enhanced the level and activation of AMPK. The levels of autophagy-related protein 5 (ATG5), Beclin-1, and LC3II/I were significantly increased by PM2.5. The activation of Unc-51-like autophagy activating kinase 1 was significantly inhibited by PM2.5. Moreover, ATG5 knockdown inhibited PM2.5-induced autophagy, ROS, and cell apoptosis significantly. The expression of cyclin D, MMP-9, and TIMP-1 was reversed by ATG5 suppression. PM2.5-induction of IL-6 and TNF-α was significantly inhibited by knockdown of ATG5. Thus, inhibition of autophagy protected the cells from PM2.5-induced injury. PM2.5 induced injury in human bronchial epithelial cells via activation of AMPK-mediated autophagy, suggesting possible therapeutic targets for the treatment of respiratory diseases.

MiR-29b-3p promotes particulate matter-induced inflammatory responses by regulating the C1QTNF6/AMPK pathway

“…Several stimuli activated the AMPK signaling pathway in different cells. Long et al found that PM2.5 increased the activation of the AMPK pathway and autophagy in bronchial epithelial cells [35]. We also found that PM 1649b exposure promoted the activation of the AMPK pathway.…”

Nrf2 positively regulates autophagy antioxidant response in human bronchial epithelial cells exposed to diesel exhaust particles

“…Lai et al 30 exposed A549 cells to DEP, urban dust and black carbon and found a significant increase in autophagy as indicated by the conversion of LC3I to LC3II. Long et al 14 demonstrated that exposure of bronchial cells to 2.5 µm PM induced autophagy by overexpressing Atg5 and beclin-1, increasing the ratio of LC3I to LC3II proteins and increasing autophagosome formation. Bai et al 12 showed that PM 1 (1 μm) at a concentration of 100 μg/mL induces autophagy and intracellular oxidative stress in type II alveolar epithelial cells in a dose-dependent manner.…”

“…One mechanism that cells use for defence against oxidative stress is autophagy, which is a homeostatic process that reduces cytoplasmic volume by degrading damaged organelles and proteins through a lysosome-dependent degradation process, and new organelles and proteins are synthesized as replacements 9-11 . Previous studies have emphasized that exposure to PM induces the generation of reactive oxygen species (ROS) and increases the levels of autophagy and cell death [12][13][14] . Some of the most harmful components of urban PM are derived from diesel exhaust particles (DEP) 15,16 .…”

Impact of Air Pollution in Airway Diseases: Role of the Epithelial Cells (Cell Models and Biomarkers)

“…A cellular defense mechanism against oxidative stress is the phenomenon of autophagy, which is a homeostatic aeration that reduces the cytoplasmic volume by degrading organelles and proteins damaged in the cell. Thus, a lysosome-dependent degradation process occurs, and new organelles and proteins are synthesized in substitution [ 118 , 119 , 120 ]. Previous studies demonstrated that the exposure to PM induces the formation of reactive oxygen species (ROS) and increases levels of autophagy and cell death [ 120 , 121 ].…”