Cigarette Smoke Impairs A2A Adenosine Receptor Mediated Wound Repair through Up-regulation of Duox-1 Expression.

Authors

Zhi Tian, University of South Florida
Hui Zhang, University of Nebraska Medical CenterFollow
Jendayi Dixon, University of South Florida
Nicole Traphagen, University of South Florida
Todd A. Wyatt, twyatt@unmc.eduFollow
Kusum K. Kharbanda, University of Nebraska Medical CenterFollow
Samantha Simet, University of Nebraska Medical CenterFollow
Narasaiah Kolliputi, University of South Florida
Diane S Allen-Gipson, University of South Florida

Document Type

Article

Journal Title

Scientific Reports

Publication Date

Spring 3-24-2017

Volume

7

Abstract

Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice. Cells were treated with 5% CS extract (CSE) for various periods of time, and mice were exposed to whole body CS for six weeks. Both CSE and CS treatment induced increased expression of Duox-1, and silencing of Doux-1 improved the rate of cell wound repair induced by CSE treatment. Nuli-1 cells pretreated with thapsigargin but not calcium ionophore exhibited increased Duox-1 mRNA expression. CSE treatment stimulated PKCα activation, which was effectively blocked by pretreatment with diphenylene iodonium, a NADPH oxidase inhibitor. Compared to control, lungs from CS-exposed mice showed a significant increase in PKCα activity and Duox-1 expression. Collectively, the data demonstrated that CS exposure upregulates expression of Duox-1 protein. This further leads to H2O2 production and PKCα activation, inhibiting A2AAR-stimulated wound repair.

DOI Link

10.1038/srep44405

ISSN

2045-2322

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Tian, Zhi; Zhang, Hui; Dixon, Jendayi; Traphagen, Nicole; Wyatt, Todd A.; Kharbanda, Kusum K.; Simet, Samantha; Kolliputi, Narasaiah; and Allen-Gipson, Diane S, "Cigarette Smoke Impairs A2A Adenosine Receptor Mediated Wound Repair through Up-regulation of Duox-1 Expression." (2017). Journal Articles: Pulmonary & Critical Care Med. 11.
https://digitalcommons.unmc.edu/com_pulm_articles/11