Modulation of Chloride Currents in Human Lung Epithelial Cells Exposed to Exogenous Oxidative Stress

Abstract

Air pollution continues to be a major public health concern affecting 9 out of 10 individuals living in urban areas worldwide. Respiratory tract is the organ most exposed to gas pollution, and ozone has been shown to be one of the most noxious pollutants to which living organisms are exposed. In the present work, we have investigated the effects of 0.1 ppm of ozone on chloride currents in human lung epithelial cells (A549 line) and whether this effect could be modulated by vitamin E pre-treatment. Whole-cell patch clamp technique was applied to not excitable cells in order to obtain information about chloride currents behavior, important for epithelial lung cells homeostasis. Significant alteration of the I-V curve after ozone treatment was observed, with the appearance of a large outward rectifier component decreasing over time and returning to the basal state levels after 24 h. Statistical analysis indicated a modification of the amount of ions passing the membrane in the unit of time as a possible cause of this difference. RT-qPCR analysis showed an increase in ClC-2 and ORCC mRNA after ozone exposure. In addition, pre-treatment with vitamin E was able to suppress the outward rectifier component induced by ozone, bringing back the current values to the control level and preventing ozone induced chloride channels up regulation. Our data suggest that ozone exposure is able to modify chloride current density and the use of vitamin E can prevent the above-mentioned damage. J. Cell. Physiol. 232: 1817-1825, 2017. © 2016 Wiley Periodicals, Inc.

Bacterial-Host Interactions: Physiology and Pathophysiology of Respiratory Infection

“…Such individuals are therefore at risk for bacterial overgrowth leading to chronic bacterial infections, in particular those caused by Pseudomonas aeruginosa (303). Similarly, air pollution and industrial exposure to irritants that alone or in combination with reactive oxygen species from oxidative stress cause an aberrant ion transport in the epithelial membrane and cytokine production that promote inflammation (56,389). Aquaporin-5 is important for fluid homeostasis in the lung, and downregulation of this aquaporin in epithelial cells in combination with an upregulation of the mucin producing gene muc5AC plays an important role in the development of viscous secretions during COPD (391).…”

Role of Nrf2 in preventing oxidative stress induced chloride current alteration in human lung cells

“…These are among the hydrophilic products able to mediate O 3 toxicity. Therefore, starting from the observation that ozone exposure of A549 cells is able to modulate chloride current (Canella et al, 2017), we have first tried to identify whether H 2 O 2 and/or 4HNE could be the responsible molecules for ozone effect.…”

“…As a follow-up of our previous work in which we were able to demonstrate that O 3 exposure is able to alter chloride currents (Canella et al, 2017), we want to better understand the byproducts that are responsible for this effect. As mentioned above, since O 3 is too reactive to penetrate the cells, the main byproducts formed by its interaction with the cellular membrane are H 2 O 2 and aldehydes, such as 4HNE.…”

“…Epithelial chloride channels play a key role in regulating the surfactant ionic composition by controlling the movements of Cl − , one of main extracellular fluid ion (Cuppoletti, Teweri, Sherry, & Malinowska, 2000). Type II cells have different chloride channel classes, among which outward rectifier chloride channel (ORCC) has been shown to be mainly involved in oxidative stress cellular response (Canella et al, 2017). ORCCs are widespread in the body (Martins, Faria, Kongsuphol, Reisch, & Schreiber, 2011) and their ability to be activated under oxidative stress has been well documented (Shimizu, Numata, & Okada, 2004).…”

Lung‐Protective Ventilation Strategies for Relief from Ventilator‐Associated Lung Injury in Patients Undergoing Craniotomy: A Bicenter Randomized, Parallel, and Controlled Trial

“…The lungs are among the key organs for development of oxidative stress [33–35]. Inspiration of high oxygen concentrations over time leads to increased oxidative stress brought about by an increase in the levels of reactive oxygen-derived free radicals, leading to generalized and localized inflammation, endothelial cell injury, and increased capillary permeability; this ultimately leads to acute lung injury, including VALI [36, 37].…”