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Volume 149, Issue 1, Pages (January 2016)

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1 Volume 149, Issue 1, Pages 62-73 (January 2016)
Oxidative and Nitrosative Stress and Histone Deacetylase-2 Activity in Exacerbations of COPD  Joseph Footitt, PhD, Patrick Mallia, PhD, Andrew L. Durham, PhD, W. Eugene Ho, PhD, Maria-Belen Trujillo-Torralbo, BSc, Aurica G. Telcian, PhD, Ajerico Del Rosario, BSc, Cheng Chang, PhD, Hong-Yong Peh, MSc, Tatiana Kebadze, MD, Julia Aniscenko, Luminita Stanciu, PhD, Sarah Essilfie-Quaye, PhD, Kazuhiro Ito, PhD, Peter J. Barnes, FCCP, Sarah L. Elkin, PhD, Onn M. Kon, MD, W. S. Fred Wong, PhD, Ian M. Adcock, PhD, Sebastian L. Johnston, PhD  CHEST  Volume 149, Issue 1, Pages (January 2016) DOI: /chest Copyright © 2016 The Authors Terms and Conditions

2 Figure 1 Time course of inflammatory cells, neutrophil elastase, and virus load in sputum during experimental rhinovirus infection. A, Total sputum inflammatory cells (neutrophils, macrophages/monocytes, lymphocytes, eosinophils). B, Sputum neutrophils. C, Sputum neutrophil elastase. D, Sputum virus load. All data are given as mean ± SEM. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001 vs baseline. †P < .05; ††P < .01 COPD vs nonsmokers. #P < .01; ##P < .01 COPD vs smokers. CHEST  , 62-73DOI: ( /chest ) Copyright © 2016 The Authors Terms and Conditions

3 Figure 2 Time course of inflammatory mediators in sputum during experimental rhinovirus infection in COPD. A, Sputum IL-1β. B, Sputum TNF-α. C, Sputum GM-CSF. D, Sputum CXCL8/IL-8. E, Sputum MMP-9. All data are given as median ± IQR. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001 vs baseline. †P < .05; ††P < .01 COPD vs nonsmokers. GM-CSF = granulocyte-macrophage colony-stimulating factor; IQR = interquartile range; MMP-9 = matrix metalloprotease-9; TNF-α = tumor necrosis factor-α. CHEST  , 62-73DOI: ( /chest ) Copyright © 2016 The Authors Terms and Conditions

4 Figure 3 Time course of oxidative and nitrosative stress markers in sputum and HDAC2 activity in sputum and BAL macrophages during experimental rhinovirus infection. A, Sputum 8-isoprostane. B, Sputum 8-hydroxy-2'-deoxyguanosine. C, Sputum 3-nitrotyrosine. D, Sputum nitrite. E, Sputum macrophage HDAC2 activity (change from baseline). F, BAL macrophage HDAC2 activity. All data are given as median ± IQR. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001 vs baseline. †P < .05; ††P < .01; †††P < .001 COPD vs nonsmokers. #P < .05; ##P < .01; ###P < .001 COPD vs smokers. HDAC2 = histone deacetylase-2. See Figure 2 legend for expansion of other abbreviation. CHEST  , 62-73DOI: ( /chest ) Copyright © 2016 The Authors Terms and Conditions

5 Figure 4 Rhinovirus infection of THP-1 cells in vitro. A, Induction of IL-6 by rhinovirus in THP-1 cells. B, Induction of CXCL-8 by rhinovirus in THP-1 cells. C, HDAC2 protein in THP-1 cells infected with rhinovirus. D, HDAC2 RNA in THP-1 cells infected with rhinovirus protein. E, HDAC2 activity in THP-1 cells infected with rhinovirus. F, HDAC2 nitrosylation in THP-1 cells infected with rhinovirus. G, Inhibition of rhinovirus-induced IL-6 by N-acetylcysteine (NAC). H, Inhibition of rhinovirus-induced CXCL8/IL-8 by NAC. Data given as mean ± SE of at least three independent experiments. ∗P < .05. CHEST  , 62-73DOI: ( /chest ) Copyright © 2016 The Authors Terms and Conditions


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