Cysteine Cathepsins: Markers and Therapy Targets in Lung Disorders

Abstract

There is now growing evidence that lung cysteine cathepsins take part in several biological processes and pulmonary homeostasis, although their exact functions remain to be clarified. Their production is increased in most tumors and in chronic and acute inflammatory lung disorders such as silicosis, COPD (emphysema, chronic bronchitis), asthma, and bronchopulmonary dysplasia. Cathepsins aggravate the extent and severity of inflammation and contribute to the remodeling and/or degradation of the extracellular matrix and the basement membrane. Cysteine cathepsins and their inhibitors (stefins and cystatins) are both potential markers of the prognosis and diagnosis of cancer. Cathepsin S is a potential marker of asthma, while cathepsin K may be a useful immunohistological marker of lymphangioleiomyomatosis and of granulomas in interstitial lung diseases. This review covers selected aspects of our current knowledge about lung cysteine cathepsins and outlines some recent advances. We also examine the implications of using cathepsin inhibitors to treat a variety of bone and joint diseases like rheumatoid arthritis, osteoporosis, and bone metastasis for the risk of deleterious side effects on the lungs.