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

(1)25-羟基维生素D3 Lα-羟基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式反应方法证明了25-羟基维生素D3 Lα-羟基酶基因在人肺泡巨噬细胞(AM)中的表达。半定量逆转录聚合酶链式反应检测结节病患者Lαhse-mR NA水平是其他肺部疾病对照组的5倍。肺泡灌洗液中LαOHSE-mRNA值与肺泡淋巴细胞相对数量、CD_4/CD_8比值、血清血管紧张素转换酶、血清离子钙及Lα、25-二羟基酶D_3/25-羟基维生素D_3(25D_3/1，25D_3)的比值均呈正相关，提示肺泡灌洗液中LαOHSE具有一定的功能，与结节病活动及钙代谢显著相关。在各种肺部疾病患者中，肺癌患者的LαOHSE-m RNA为…。更显著的增强，大约是对照的两倍。LαOHSE基因水平与25D3/I、25D3比值呈正相关。虽然没有统计学意义，但在晚期患者AM中α的表达水平有升高的趋势。(2)过氧化体增殖物激活受体T在人肺巨噬细胞中的表达和功能PPARα，β和γ均有表达，但以PPARγ为主。PPARγ的特异性配体15-脱氧-D12，14-前列腺素J2(15d-PGJ2)可显著降低内毒素诱导的AM产生的α，并显著增加CD36的表达，CD36的表达介导了中性粒细胞对凋亡的吞噬，这是炎症消退的重要过程。我们通过体外吞噬实验证实，15d-PGJ2处理的Ams对凋亡的中性粒细胞的吞噬能力显著增强。结果表明，AM中PPARγ通过抑制细胞因子的产生，增强其吞噬凋亡中性粒细胞的能力，从而发挥抗炎作用。较少

(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