THE STUDY OF THE EXPRESSIONS AND FUNCTIONS OF NUCLEAR HORMONE RECEPTORS IN HUMAN ALVEOLAR MACROPHAGES

(1) 25-羟基维生素D3 lα-羟化酶基因在人肺泡巨噬细胞中的表达我们用逆转录聚合酶链反应（RT-PCR）证实了25-羟基维生素D3 lα-羟化酶（lαOHse）基因在支气管肺泡灌洗细胞制备的人肺泡巨噬细胞（AM）中的表达。半定量RT-PCR检测结节病患者的lα Hse-mRNA水平是其他肺部疾病对照患者的5倍。支气管肺泡灌洗液中lα Ohse- mrna水平与肺泡淋巴细胞相对数量、CD4/CD8比值、血清ACE、血清离子钙及lα， 25-二羟化酶D3/25-羟基维生素D3 （25D3/ 1,25d3）比值具有良好的相关性，提示AM中lα Ohse具有功能性，且与结节病活性及钙代谢显著相关。在各种肺部疾病患者中，我们发现肺癌患者的lα ose - mrna明显升高，约为对照组的两倍。lα Ohse-mRNA水平与25D3/I，25D3比值呈正相关。AM晚期患者的lα Ohse-mRNA水平有升高的趋势，但无统计学意义。(2)过氧化物酶体增殖物激活受体（PPAR） T在人肺泡巨噬细胞中的表达及功能利用RT-PCR技术，我们证实了PPAR mrna在新鲜分离的人AM中的表达。PPARα、β和γ均有表达，但以PPARγ为主。PPARγ， 15-脱氧- d12,14前列腺素J2 （15d-PGJ2）的特异性配体显著降低lps诱导的Ams产生TNF-α，并显著增加CD36的表达，CD36介导凋亡中性粒细胞的吞噬，这是解决炎症的重要过程。我们通过体外吞噬实验证实，15d- pgj2处理的Ams对凋亡中性粒细胞的吞噬能力显著增加。这些数据表明，am中的PPARγ通过抑制细胞因子的产生和增加CD36的表达以及增强吞噬凋亡的嗜中性粒细胞的能力来发挥抗炎作用。少

(1) Expression of the 25-hydroxyvitamin D3 lα-hydroxylase gene in human alveolar macrophagesWe demonstrated expression of the 25-hydroxyvitamin D3 lα-hydroxylase (lαOHse) gene in human alveolar macrophages (AM) prepared from bronchoalveolar lavage cells by reverse transcription polymerase chain reaction (RT-PCR). The lα Hse-mRNA level measured by semiquantitative RT-PCR was five-fold higher in patients with sarcoidosis than control patients with other pulmonary disorders. There was a good correlation between the lα Ohse-mRNA level in bronchoalveolar lavage samples and the relative population of alveolar lymphocytes, the CD4/CD8 ratio, serum ACE, serum ionized calcium and the lα, 25-dihydroxylase D3/25-hydroxyvitamin D3 (25D3/1,25D3) ratio, suggesting that lα Ohse in AM was functional and significantly correlated with the activity of sarcoidosis and calcium metabolism.Among patients with various pulmonary diseases, we found that the lα Ohse-mRNA in patients with lung carcinomas was sign … More ificantly enhanced, about twice the control. Correlation was observed between lα Ohse-mRNA level and the 25D3/I,25D3 ratio. Though not statistically significant, the lα Ohse-mRNA level in AM tended to increase in the patients with advanced stage.(2) Expression and Function of Peroxisome Proliferator-Activated Receptor (PPAR) T in Human Alveolar MacrophagesUsing RT-PCR, we demonstrated the expression of PPAR mRNAs in freshly isolated human AM. PPARα, β and γ were all expressed, but PPARγ was dominant. A specific ligand of PPARγ, 15-deoxy-D12,14prostaglandin J2 (15d-PGJ2), significantly decreased LPS-induced TNF-α production by Ams and markedly increased the expression of CD36 that mediates the phagocytosis of apoptotic neutrophils, an essential process for the resolution of inflammation. We confirmed that 15d-PGJ2-treated Ams showed a significantly increased phagocytosis of apoptotic neutrophils by in vitro phagocytosis assay. The data indicate that PPARγ in Ams play an anti-inflammatory role through inhibiting cytokine production and increasing their CD36 expression with the enhancement of the capacity to phagocytose apoptotic neulrophils. Less