Oxidative and Nitrosative Stress and Histone Deacetylase-2 Activity in Exacerbations of COPD
Abstract
BACKGROUND: Respiratory virus infections are commonly associated with COPD exacerbations, but little is known about the mechanisms linking virus infection to exacerbations. Pathogenic mechanisms in stable COPD include oxidative and nitrosative stress and reduced activity of histone deacetylase-2 (HDAC2), but their roles in COPD exacerbations is unknown. We investigated oxidative and nitrosative stress (O&NS) and HDAC2 in COPD exacerbations using experimental rhinovirus infection. METHODS: Nine subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II), 10 smokers, and 11 nonsmokers were successfully infected with rhinovirus. Markers of O&NS-associated cellular damage, and inflammatory mediators and proteases were measured in sputum, and HDAC2 activity was measured in sputum and bronchoalveolar macrophages. In an in vitro model, monocyte-derived THP-1 cells were infected with rhinovirus and nitrosylation and activity of HDAC2 was measured. RESULTS: Rhinovirus infection induced significant increases in airways inflammation and markers of O&NS in subjects with COPD. O&NS markers correlated with virus load and inflammatory markers. Macrophage HDAC2 activity was reduced during exacerbation and correlated inversely with virus load, inflammatory markers, and nitrosative stress. Sputum macrophage HDAC2 activity pre-infection was inversely associated with sputum virus load and inflammatory markers during exacerbation. Rhinovirus infection of monocytes induced nitrosylation of HDAC2 and reduced HDAC2 activity; inhibition of O&NS inhibited rhinovirus-induced inflammatory cytokines. CONCLUSIONS: O&NS, airways inflammation, and impaired HDAC2 may be important mechanisms of virus-induced COPD exacerbations. Therapies targeting these mechanisms offer potential new treatments for COPD exacerbations.
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BibTeX
@article{footitt2026oxidative,
title = {{Oxidative and Nitrosative Stress and Histone Deacetylase-2 Activity in Exacerbations of COPD}},
author = {Joseph Footitt and Patrick Mallia and Andrew Durham and W. Eugene Ho and Maria-Belen Trujillo-Torralbo and Aurica Telcian and Ajerico del Rosario and Cheng Chang and Hong-Yong Peh and Tatiana Kebadze and Julia Aniscenko and Luminita Stanciu and Sarah Essilfie-Quaye and Kazuhiro Ito and Peter Barnes and Sarah Elkin and Onn Kon and W. Wong and Ian Adcock and Sebastian Johnston},
journal = {Chest},
year = {2026},
month = oct,
doi = {10.1378/chest.14-2637},
url = {https://hal.science/hal-05787802v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Oxidative and Nitrosative Stress and Histone Deacetylase-2 Activity in Exacerbations of COPD
AU - Joseph Footitt
AU - Patrick Mallia
AU - Andrew Durham
AU - W. Eugene Ho
AU - Maria-Belen Trujillo-Torralbo
AU - Aurica Telcian
AU - Ajerico del Rosario
AU - Cheng Chang
AU - Hong-Yong Peh
AU - Tatiana Kebadze
AU - Julia Aniscenko
AU - Luminita Stanciu
AU - Sarah Essilfie-Quaye
AU - Kazuhiro Ito
AU - Peter Barnes
AU - Sarah Elkin
AU - Onn Kon
AU - W. Wong
AU - Ian Adcock
AU - Sebastian Johnston
PY - 2026
DA - 2026/10/09
JO - Chest
DO - 10.1378/chest.14-2637
UR - https://hal.science/hal-05787802v1
AB - BACKGROUND: Respiratory virus infections are commonly associated with COPD exacerbations, but little is known about the mechanisms linking virus infection to exacerbations. Pathogenic mechanisms in stable COPD include oxidative and nitrosative stress and reduced activity of histone deacetylase-2 (HDAC2), but their roles in COPD exacerbations is unknown. We investigated oxidative and nitrosative stress (O&NS) and HDAC2 in COPD exacerbations using experimental rhinovirus infection. METHODS: Nine subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II), 10 smokers, and 11 nonsmokers were successfully infected with rhinovirus. Markers of O&NS-associated cellular damage, and inflammatory mediators and proteases were measured in sputum, and HDAC2 activity was measured in sputum and bronchoalveolar macrophages. In an in vitro model, monocyte-derived THP-1 cells were infected with rhinovirus and nitrosylation and activity of HDAC2 was measured. RESULTS: Rhinovirus infection induced significant increases in airways inflammation and markers of O&NS in subjects with COPD. O&NS markers correlated with virus load and inflammatory markers. Macrophage HDAC2 activity was reduced during exacerbation and correlated inversely with virus load, inflammatory markers, and nitrosative stress. Sputum macrophage HDAC2 activity pre-infection was inversely associated with sputum virus load and inflammatory markers during exacerbation. Rhinovirus infection of monocytes induced nitrosylation of HDAC2 and reduced HDAC2 activity; inhibition of O&NS inhibited rhinovirus-induced inflammatory cytokines. CONCLUSIONS: O&NS, airways inflammation, and impaired HDAC2 may be important mechanisms of virus-induced COPD exacerbations. Therapies targeting these mechanisms offer potential new treatments for COPD exacerbations.
SN - 0012-3692
SN - 1931-3543
ER -