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Title: Peroxiredoxin 6 differentially regulates acute and chronic cigarette smoke–mediated lung inflammatory response and injury.

Authors: Sundar, Isaac K; Chung, Sangwoon; Hwang, Jae-Woong; Arunachalam, Gnanapragasam; Cook, Suzanne; Yao, Hongwei; Mazur, Witold; Kinnula, Vuokko L; Fisher, Aron B; Rahman, Irfan

Published In Exp Lung Res, (2010 Oct)

Abstract: Peroxiredoxin 6 (Prdx6) exerts its protective role through peroxidase activity against H₂O₂ and phospholipid hydroperoxides. We hypothesized that targeted disruption of Prdx6 would lead to enhanced susceptibility to cigarette smoke (CS)-mediated lung inflammation and/or emphysema in mouse lung. Prdx6 null (Prdx6⁻/⁻mice exposed to acute CS showed no significant increase of inflammatory cell influx or any alterations in lung levels of proinflammatory cytokines compared to wild-type (WT) mice. Lung levels of antioxidant enzymes were significantly increased in acute CS-exposed Prdx6⁻/⁻ compared to WT mice. Overexpressing (Prdx6⁻/⁻) mice exposed to acute CS showed significant decrease in lung antioxidant enzymes associated with increased inflammatory response compared to CS-exposed WT mice or air-exposed Prdx6⁻/⁻ mice. However, chronic 6 months of CS exposure resulted in increased lung inflammatory response, mean linear intercept (Lm), and alteration in lung mechanical properties in Prdx6⁻/⁻ when compared to WT mice exposed to CS. These data show that targeted disruption of Prdx6 does not lead to increased lung inflammatory response but is associated with increased antioxidants, suggesting a critical role of lung Prdx6 and several compensatory mechanisms during acute CS-induced adaptive response, whereas this protection is lost in chronic CS exposure leading to emphysema.

PubMed ID: 20939758 Exiting the NIEHS site

MeSH Terms: Acute Disease; Animals; Bronchoalveolar Lavage Fluid/cytology; Cell Count; Chemokine CCL2/metabolism; Chronic Disease; Lung/drug effects; Lung/metabolism; Lung/pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Peroxiredoxin VI/deficiency; Peroxiredoxin VI/genetics; Peroxiredoxin VI/metabolism*; Pneumonia/etiology; Pneumonia/metabolism*; Pneumonia/pathology; Smoking/adverse effects*; Tobacco Smoke Pollution/adverse effects*

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