Differential Expression of The Lactate Dehydrogenase-A and B Subunit Genes in Lung Cells in Interstitial Pneumonia and Pulmonary Fibrosis

特发性间质性肺炎(IIP)在欧美国家也称为特发性肺纤维化，是一种病因不明的疾病，表现为下呼吸道和肺泡内不受控制的慢性炎症过程。在反映疾病活动性的多种参数中，血清乳酸脱氢酶(LDH)水平被确定为一个重要的指标。在包括人类在内的哺乳动物中，LDH的五种体细胞同工酶是A(肌肉)和B(心脏)亚基的四聚体组合。血清LDH升高在IIP急性加重期或急性起病的间质性肺炎时尤为显著，且血清中异四聚体同工酶II(H3M1或A1B3)通常升高。然而，在分子水平上对乳酸脱氢酶活性升高的机制(S)却知之甚少，本课题旨在阐明…的分子机制更多(S)在肺泡上皮细胞、肺成纤维细胞或肺泡巨噬细胞等肺细胞中LDH-A和-B亚单位基因差异表达的调控。首先，在1993学年，我们分别从肺成纤维细胞和外周血单核细胞中提取了LDH-A和LDH-B亚基基因的cDNAs，并用特异的寡核苷酸引物进行了PCR扩增。1994年，我们开始研究PMA、IL-1β、TNF-α等特异性刺激条件下上述两种基因在上述肺细胞中的差异表达。这些研究仍在进行中，我们希望了解(S)升高血清LHD水平的机制。此外，进一步的实验计划正在考虑中，以评估在转录或转录后水平上LDH-A和-B亚单位基因差异表达的调节。此外，利用来自IIP患者的人肺组织进行的基因表达的原位杂交研究正在进行中。较少

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 … More (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