Long-term exposure to cigarette smoke impairs lung function and increases HMGB-1 expression in mice.

Abstract

Cigarette smoke (CS)-induced emphysema is caused by a continuous inflammatory response in the lower respiratory tract. The development of the condition is believed to be mediated by oxidant–antioxidant imbalance. This paper describes the effects of long-term CS exposure on alveolar cell recruitment, antioxidant defense systems, activity of extracellular matrix metalloelastases, expression of metalloelastase MMP-12, and high mobility group box-1 protein (HMGB-1). Ten C57Bl/6 mice were exposed to 12 cigarettes-a-day for 60 consecutive days, while 10 control animals were exposed to ambient air. After sacrifice, bronchoalveolar lavage fluid (BALF) was removed, and lung tissue underwent biochemical and histological analyses. In CS-exposed animals influx of alveolar macrophages and neutrophils into BALF, lung static elastance, and expression of MMP-12 and HMGB-1 were significantly increased while the activity of antioxidant enzyme was significantly reduced in comparison with control group. Thus, we demonstrated for the first time that long-term CS exposure decreased antioxidant defenses concomitantly with impaired lung function, which was associated with HMGB-1 expression.