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

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(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