Development of therapeutic ways on various pathological features in chronic obstructive pulmonary diseases

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Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity in the world. However, there are only a few therapeutic drugs for the treatment of this disease. To evaluate new pharmacological approaches for COPD, it is necessary to make progress in understanding lung physiology and pathophysiology of COPD. The findings in this study were summarized below.1. We have found that myeloid Elf-1 like factor (MEF) regulated the differentiation of airway epithelial cells. In addition to this, MEF-transfected carcinoma cells did not grow. Therefore, we proposed that MEF act as not only a differentiation regulator, but also a tumor suppressor.2. We found that GM-CSF mRNA expression was upnregulated by ETS-2 transcription factor in adenocarcinoma cells, and was a target of protein kinase C.3. We have found some new drugs to control mucous secretion in airway diseases. Among them, fudosteine, a new cysteine derivative, inhibited the formation of airway goblet cells, and glycyrrhizin, inhibited mucus production by enhancing the effect of glucocorticoids.4. We have found new endogenous pulmonary surfactant secretagogues, adrenomedullin and prostaglandin E_2. We also found that there is a synergistic cross-talk between protein kinase A- and protein kinase C-dependent signalings in alveolar type II cells.