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John-Schuster, Gerrit; Günter, Stefanie; Hager, Katrin; Conlon, Thomas M.; Eickelberg, Oliver und Yildirim, Ali Önder (2016): Inflammaging increases susceptibility to cigarette smoke-induced COPD. In: Oncotarget, Bd. 7, Nr. 21: S. 30068-30083

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Abstract

Chronic obstructive pulmonary disease (COPD) is related to an abnormal chronic inflammatory response of the lung to mainly cigarette smoke (CS) and the disease risk is increased in aged individuals. The source of this chronic inflammation is due to the repeated and progressive activation of immune cells. We hypothesize that in a chronic CS-induced mouse model, the predisposition to COPD pathogenesis in aged mice is characterized by an elevated immune response compared to young animals. We measured several characteristics of COPD in young and old mice (2 and 12 months of age) exposed to CS for 3 months. CS-exposed aged mice exhibited increased lung compliance (0.061 +/- 0.008 vs. 0.055 +/- 0.006 ml/cm H2O, p < 0.01), emphysema development (35.36 +/- 0.71 vs. 25.31 +/- 0.005 mu m;p < 0.01) and airway remodeling (2.15 +/- 0.37 vs. 1.09 +/- 0.64 mu m(3)/mu m(2);p < 0.01) compared to control animals, which was not seen in CS-exposed young mice. Quantification of lung tissue inflammation revealed a significantly greater volume of inducible bronchus-associated lymphoid tissue structures in aged mice after CS exposure (5.94 +/- 2.89 vs. 2.37 +/- 1.69 mu m(3)/mu m(2);p < 0.01). Our results indicate that age-induced lung inflammation is further elevated after CS exposure in old mice, potentially via an age-induced change in immune cell susceptibility to CS thereby accelerating the pathophysiological hallmarks of COPD.

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