Despite the magnitude of the public health consequences, little is known about the mechanisms involved in ambient Particular Matter (PM) induced cardiopulmonary diseases. Our preliminary data shows that PM causes disruption of the alveolar epithelial barrier by affecting tight junction proteins, specifically Occludin and Zona Occludens-1 (ZO-1). This effect is mediated by the increase in reactive oxygen species (ROS) production and PKC-zeta (PKC-ζ) activation.
In this study, primary rat alveolar type II (ATII) cells and human lung adenocarcinoma (A549) cells were treated with PM and diesel exhaust particles (DEP), plasma membrane proteins were isolated and analyzed by western blot. C57/BL6 mice were intubated and instilled intratracheally with saline or saline containing 200ug of Titanium Oxide (TiO2), PM or DEP. After 6 and 24 hours, bronchoalveolar lavage fluid (BALF) was collected and plasma membrane from lung tissue was isolated and analyzed by western blot.
PM and DEP exposures caused a decrease in occludin abundance at the plasma membrane with no changes in neither E-cadherin or claudin 3 and 5, in alveolar epithelial cells (AEC). These results were similar in mouse lungs. In BALF from PM and DEP treated mice, we found an increased protein concentration and inflammatory cell count, with a predominance of neutrophils, compared to Control and TiO2 groups. Pre-treatment of mice with PKC-ζ inhibitor prevented PM induced increase in lung inflammation. In parallel, PKC-ζ inhibitor preserved occludin at the plasma membrane in mouse lungs, and in AEC.
PKC-ζ is involved in PM-induced occludin reduction at the plasma membrane in the alveolar epithelium. Inhibition of PKC-ζ protects against PM-induced lung inflammation.
A better understanding of the mechanisms implicated in PM-induced lung injury will provide future therapeutic strategies that could decrease the morbidity and mortality associated with high concentration levels of PM.
Juan Caraballo, No Financial Disclosure Information; No Product/Research Disclosure Information