Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with progressive airflow obstruction. Tobacco smoking is the main risk factor worldwide. In contrast to asthma, anti-inflammatory therapies are rather ineffective in improving chronic symptoms and reducing inflammation, lung function decline, and airway remodeling. Specific drugs that are directed against the remodeling and chronic inflammation, thereby preventing lung tissue damage and progressive lung function decline, must be developed. Experimental models and expression studies suggest that anti-vascular endothelial growth factor (VEGF) receptor strategies may be of use in patients with emphysema, whereas anti-HER1-directed strategies may be more useful in patients with pulmonary mucus hypersecretion, as seen in chronic bronchitis and asthma.
Growth factors and cytokines including VEGF, fibroblast growth factors, transforming growth factor-β, tumor necrosis factor-α, CXCL1, CXCL8, and CCL2, and signal transduction proteins such as mitogen-activated protein kinase p38 and nuclear factor-⦊B, seem to be important pathogenetic molecules in COPD. Specific antagonists for these proteins may be effective for different inflammatory diseases. However, their efficacy for COPD therapy has not yet been demonstrated. Finally, other drugs such as retinoic acids may provide restoration of lung tissue structure. Such approaches, however, must await the first results of growth factor or cytokine antagonist therapy in chronic lung diseases.
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de Boer, W.I., Alagappan, V.K.T. & Sharma, H.S. Molecular mechanisms in chronic obstructive pulmonary disease. Cell Biochem Biophys 47, 131–147 (2007). https://doi.org/10.1385/CBB:47:1:131
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DOI: https://doi.org/10.1385/CBB:47:1:131