Abstract
COPD is considered the major growing cause of mortality and morbidity worldwide, and it is going to become the third most common cause of death by 2020. Presently, there are about 200 million people suffering from some degree of COPD in the entire world. Animal models are very important to get insights into the pathogenesis of COPD. However, the currently available cigarette smoke-induced COPD models usually take a long time to develop and are reversible after stopping the stimuli. The need of a new model is compelling. In the present study we focus on the role of matrix metalloproteinases in the pathogenesis of COPD and hypothesized that overexpression of MMP-2 in lungs would allow the development of COPD in a short term after cigarette smoke inhalation. We developed a novel MMP-2 transgenic mouse that can express high level of the human MMP-2 in the lungs. COPD was induced by inhalation of cigarette smoking extract (CSE) for two weeks in wild type (WT/CSE) C57BL/6 and human MMP-2 transgenic mice (MMP-2/CSE). Mice that inhaled saline (WT/SAL & MMP-2/SAL) were used as control groups. The MMP-2 transgenic mice expressed high levels of MMP-2 in the lungs. They showed no phenotype in unstressed conditions. MMP-2/CSE showed significant emphysematous changes in the lungs compared to WT/CSE and MMP-2/SAL groups after 2-week inhalation of CSE. The lung of MMP-2/CSE mice showed significantly increased infiltration of inflammatory cells and increased level of inflammatory cytokines compared to control mice. This novel mouse model of COPD will be a very useful tool for evaluating the mechanistic pathways and for the development of novel therapies in cigarette smoke-associated COPD.
- © 2014 ERS
