Sun Xiaocun, Zemel Michael B
Department of Nutrition, University of Tennessee, Knoxville, TN 37996-1900, USA.
J Nutr Biochem. 2008 Jun;19(6):392-9. doi: 10.1016/j.jnutbio.2007.05.013. Epub 2007 Sep 14.
The objective of this study was to investigate the effects of calcitriol on adipocyte and macrophage cytokine expression as well as release and on adipocyte-macrophage cross-talk in local modulation of inflammation.
We investigated calcitriol modulation of the expression of macrophage inhibitory factor (MIF) and macrophage surface-specific protein CD14, two key factors in regulating macrophage function and survival, in differentiated human adipocytes. Calcitriol significantly increased MIF and CD14 expression by 59% and 33%, respectively, while calcium-channel antagonism with nifedipine completely reversed these effects, indicating that calcitriol stimulates MIF and CD14 expression via a calcium-dependent mechanism. Similar results were also found in cultured 3T3-L1 adipocytes; in addition, calcitriol also up-regulated macrophage colony-stimulating factor, macrophage inflammatory protein, interleukin-6 (IL-6) as well as monocyte chemoattractant protein-1 expression in 3T3-L1 adipocytes and stimulated tumor necrosis factor as well as IL-6 expression in RAW 264 macrophages. These effects were blocked by either a calcium-channel antagonist (nifedipine) or a mitochondrial uncoupler (dinitrophenol). Moreover, co-culture of 3T3-L1 adipocytes with RAW 264 macrophages significantly increased the expression and production of multiple inflammatory cytokines in response to calcitriol in both cell types.
These data demonstrate that calcitriol regulates local inflammation via modulating the interaction between adipocytes and macrophages as well as regulating inflammatory cytokine production in each cell type via calcium-dependent and mitochondrial uncoupling-dependent mechanisms. These data provide further mechanistic explanation for our recent observations that suppression of calcitriol by dietary calcium reduces inflammatory cytokine expression and oxidative stress in adipose tissue.
本研究旨在探讨骨化三醇对脂肪细胞和巨噬细胞细胞因子表达及释放的影响，以及对脂肪细胞 - 巨噬细胞在局部炎症调节中的相互作用的影响。
我们研究了骨化三醇对分化的人脂肪细胞中巨噬细胞抑制因子（MIF）和巨噬细胞表面特异性蛋白CD14表达的调节作用，这两个是调节巨噬细胞功能和存活的关键因子。骨化三醇分别使MIF和CD14表达显著增加59%和33%，而硝苯地平的钙通道拮抗作用完全逆转了这些效应，表明骨化三醇通过钙依赖性机制刺激MIF和CD14表达。在培养的3T3 - L1脂肪细胞中也发现了类似结果；此外，骨化三醇还上调了3T3 - L1脂肪细胞中巨噬细胞集落刺激因子、巨噬细胞炎性蛋白、白细胞介素 - 6（IL - 6）以及单核细胞趋化蛋白 - 1的表达，并刺激RAW 264巨噬细胞中肿瘤坏死因子以及IL - 6的表达。这些效应被钙通道拮抗剂（硝苯地平）或线粒体解偶联剂（二硝基苯酚）阻断。此外，3T3 - L1脂肪细胞与RAW 264巨噬细胞共培养显著增加了两种细胞类型中对骨化三醇反应的多种炎性细胞因子的表达和产生。
这些数据表明，骨化三醇通过调节脂肪细胞与巨噬细胞之间的相互作用以及通过钙依赖性和线粒体解偶联依赖性机制调节每种细胞类型中的炎性细胞因子产生来调节局部炎症。这些数据为我们最近的观察结果提供了进一步的机制解释，即饮食钙对骨化三醇的抑制可降低脂肪组织中的炎性细胞因子表达和氧化应激。
