Cholesteryl ester transfer protein (CETP) is a target gene for the liver X receptor (LXR). The aim of this study was to further explore this regulation in the monocyte-macrophage lineage and its ...modulation by lipid loading and inflammation, which are key steps in the process of atherogenesis.
Exposure of bone marrow-derived macrophages from human CETP transgenic mice to the T0901317 LXR agonist increased CETP, PLTP, and ABCA1 mRNA levels. T0901317 also markedly increased CETP mRNA levels and CETP production in human differentiated macrophages, whereas it had no effect on CETP expression in human peripheral blood monocytes. In inflammatory mouse and human macrophages, LXR-mediated CETP gene upregulation was inhibited, even though ABCA1, ABCG1, and SREBP1c inductions were maintained. The inhibition of CETP gene response to LXR agonists in inflammatory cells was independent of lipid loading (ie, oxidized LDL increased CETP production in noninflammatory macrophages with a synergistic effect of synthetic LXR agonists).
LXR-mediated induction of human CETP expression is switched on during monocyte-to-macrophage differentiation, is magnified by lipid loading, and is selectively lost in inflammatory macrophages, which suggests that inflammatory cells may not increase the circulating CETP pool on LXR agonist treatment.
We have successfully synthesized the highly c-axis-oriented polycrystals of apatite-type lanthanum silicate by the reactive diffusion technique. When the La2SiO5/La2Si2O7 diffusion couples were ...isothermally heated at 1773 K - 1873 K for 5 h - 100 h, the apatite polycrystals readily produced in the form of layer at the interfacial boundaries. The annealed couples were characterized using optical microscopy, micro-Raman spectroscopy, X-ray diffractometry and electron probe microanalysis. The product layers were composed of the highly c-axis-oriented prismatic crystallites, with their elongation directions being almost parallel to the diffusion direction. The formation of the apatite layer was controlled by volume diffusion, the overall reaction of which is described by (10+6x)La2SiO5 + (4-3x)La2Si2O7 → 3La9.33+2x(SiO4)6O2+3x (0.01 ≤ x ≤ 0.13). The apatite layer formed at 1873 K was characterized by the steady decrease of the x-value along the diffusion direction from 0.13 at the La2SiO5/apatite interface to 0.01 at the apatite/La2Si2O7 interface. We have also prepared the sandwich-type La2Si2O7/La2SiO5/La2Si2O7 diffusion couples and heated at 1873 K for 100 h. The annealed couple was mechanically processed and the thin-plate electrolyte consisting of the highly c-axisoriented polycrystal was obtained. The oxide-ion conductivity was determined from the impedance spectroscopy data at 573 K - 973 K, which steadily increased from 2.4 × 10-3 S/cm to 2.39 × 10-2 S/cm with increasing temperature. The empirical activation energy of conduction was 0.35 eV, which compares well with the calculated migration energy of 0.32 eV in a previous study.
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