Cigarette Smoke Impairs A 2A Adenosine Receptor Mediated Wound Repair through Up-regulation of Duox-1 Expression

Zhi Tian, Hui Zhang, Jendayi DIxon, Nicole Traphagen, Todd A. Wyatt, Kusum Kharbanda, Samantha Simet Chadwick, Narasaiah Kolliputi, DIane S. Allen-Gipson

Research output: Contribution to journalArticle

4 Scopus citations

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 A 2A AR-stimulated wound repair.

Original languageEnglish (US)
Article number44405
JournalScientific reports
Volume7
DOIs
StatePublished - Mar 24 2017

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