Modulation of Matrix Metalloproteinase Activity by Tobacco Cigarette Smoke

Tobacco smoking is a highly addictive social behavior and a major cause of morbidity and mortality. It causes or exacerbates a multitude of pathological conditions and in both the adult and the fetus may have various detrimental effects. Tobacco smoke contains more than 4000 chemicals including a huge repertoire of addictive and/or toxic components including nicotine, benzene, cadmium, vinyl chloride, chromium and 2-naphthylamine, all of which are recognized carcinogens (WHO). All of these agents have been implicated in a myriad of pathological conditions. Nevertheless the mechanisms by which tobacco smoke induces these pathological changes is not clear. Several areas of particular relevance relate to smoke-induced connective tissue alterations and of course genetic changes. In the case of the former, smokeinduced skin and oral cavity related alterations in connective tissue have received some attention. In both cases matrix metalloproteinases (MMPs) are implicated in tissue degradation and reduced collagen synthesis. While such changes may not be life threatening, other smoke induced changes in organs such as the lungs or heart carry with them potential for significant increases in mortality or morbidity. The direct exposure endured by the lungs to inhaled smoke, whether as primary smoke from the cigarette or as secondary from the environment, now generally termed passive smoking, may be associated with altered MMP gene expression in lung airway epithelium and be related to development of chronic obstructive pulmonary disease or asthma. The present review will provide background on structure and function of the MMPs and examine the evidence that tobacco smoke alters MMP gene expression and MMP activity and the role these changes may play in connective tissue changes in tissues and cells. We will also discuss ongoing work in our laboratory which is directed to determining smoke-induced alterations in MMP release particularly in lung cells.