Conclusion
This study demonstrates that the impact of MT on airway epithelia by suppressing oxidative stress and maintaining metal ion homeostasis is beneficial in attenuating damage to pulmonary cells undergoing PM exposure.
Methods
A combination of omics technology and bioinformatic analysis were used to uncover mechanisms underlying cellular responses to PM exposure in human bronchial epithelia (HBE) cells and imply the potential rescue.
Purpose
To investigate the mechanism underlying particulate matter (PM) exposure-induced oxidative stress and potential rescue strategies against pulmonary damage in this context.
Results
Our results implicated that oxidative stress, metal ion homeostasis, and apoptosis were the major cellular responses to PM exposure in HBE cells. PM exposure disrupted oxidative phosphorylation (OXPHOS)-related gene expressions in HBE cells. Rescuing the expression of these genes with supplemental coenzyme Q10 (Co Q10) inhibited reactive oxygen species (ROS) generation; however, it only partially protected HBEs against PM exposure-induced apoptosis. Further, metallothionein (MT)-encoding genes associated with metal ion homeostasis were significantly induced in HBE cells, which was transcriptionally regulated by specificity protein 1 (SP1). SP1 knock-down (KD) aggravated PM-induced apoptosis in HBE cells, suggesting it plays a role in MT induction. Subsequent studies corroborated the protective role of MT by showing that exogenous MT supplement demonstrated effective protection against PM-induced oxidative stress and apoptosis in HBE cells. Importantly, exogenous MT supplement was shown to reduce ROS generation and apoptosis in airway epithelia in both HBE cells and a PM-inhaled murine model.