| Budget Amount *help |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Research Abstract |
Idiopathic interstitial pneumonia (IIP), which is also referred to as idiopathic pulmonary fibrosis in US and European countries, is considered to be the disease with unknown etiology that is manifested by an uncontrolled and chronic inflammatory process in the lower respiratory tract and alveoli of the lung. Among a variety of parameters that reflect the activity of the disease, the serum level of lactate dehydrogenase (LDH) is established as an important indicator. In mammals including human, the five somatic isozymes of LDH are the tetrameric combinations of the A (muscle) and B (heart) subunits. The elevation of serum LDH is particularly significant in the condition of acute exacerbation of IIP or acute-onset interstitial pneumonia, and the heterotetrameric isozyme II (H3M1 or A1B3) usually elevates in serum. However, little is known about the mechanism (s) of elevation of LDH activity in the disease at the molecular level.
This project is aimed to elucidate the molecular mechanism
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(s) of regulation of differential expression of LDH-A and-B subunit genes in lung cell such as alveolar epithelial cells, lung fibroblasts, or alveolar macrophages. First, in the academic year of 1993, we cloned both cDNAs of the genes for LDH-Aand-B subunits by using reverse transcription of mRNA from lung fibroblasts and blood mononuclear cells, respectively, and PCR amplification with the specific oligonucleotide primers. In the year of 1994, we heve started to study differential expression of both genes in the above lung cells in the absence or presence of specific stimuli such as PMA,IL-1beta, or TNF-alpha. These studies are on going and we expect to understand the mechanism (s) in elevation of serum LHD levels. Also, further experimental plans are under consideration to evaluate the regulation in differential expression of LDH-A and-B subunit genes at the transcriptional or post-transcriptional level. In addition, in situ hybridization study for expression of the genes using human lung tissues from individuals with IIP is underway. Less
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