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We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. 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 PKC\u03b1 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 PKC\u03b1 activity and Duox-1 expression. Collectively, the data demonstrated that CS exposure upregulates expression of Duox-1 protein. This further leads to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> production and PKC\u03b1 activation, inhibiting A<jats:sub>2A<\/jats:sub>AR-stimulated wound repair.<\/jats:p>","DOI":"10.1038\/srep44405","type":"journal-article","created":{"date-parts":[[2017,3,24]],"date-time":"2017-03-24T11:06:28Z","timestamp":1490353588000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cigarette Smoke Impairs A2A Adenosine Receptor Mediated Wound Repair through Up-regulation of Duox-1 Expression"],"prefix":"10.1038","volume":"7","author":[{"given":"Zhi","family":"Tian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jendayi","family":"Dixon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Traphagen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd A.","family":"Wyatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kusum","family":"Kharbanda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Simet Chadwick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narasaiah","family":"Kolliputi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane S.","family":"Allen-Gipson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,3,24]]},"reference":[{"key":"BFsrep44405_CR1","first-page":"(2009), A2382","volume":"179","author":"D Allen-Gipson","year":"2009","unstructured":"Allen-Gipson, D., Jarrell, J. 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