Stanniocalcin-1, an inhibitor of macrophage chemotaxis and chemokinesis
Stanniocalcin-1, an inhibitor of macrophage chemotaxis and chemokinesis
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DOI：
10.1152/ajprenal.00138.2003
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发表时间：
2004-02-01
影响因子：
4.2
通讯作者：
Sheikh-Hamad, D
中科院分区：
文献类型：
--
作者：
Kanellis, J;Bick, R;Sheikh-Hamad, D
在巨噬细胞中，细胞内钙的变化与调节细胞粘附和运动性的细胞过程的激活有关，并且对于巨噬细胞对抗原刺激的反应是重要的。鱼类钙调节激素斯钙素-1（STC 1）的哺乳动物对应物在包括胸腺和脾脏在内的多个器官中表达，因此，我们假设它可能在调节免疫/炎症反应中发挥作用。利用小鼠巨噬细胞样（RAW264.7）和人单核细胞样（U937）细胞研究体外趋化性，我们发现STC 1减弱了趋化作用，并减少了对单核细胞趋化蛋白-1（MCP-1）和基质细胞衍生因子-1 α的趋化反应。与这些发现一致，STC 1减弱了MCP-1刺激RAW 264.7细胞后细胞内钙的升高。在体内研究表明，STC 1的差异表达在阻塞的肾脏和定位到巨噬细胞。MCP-1和STC 1的转录都上调后输尿管梗阻，这表明两个基因之间的功能关联。我们的数据表明哺乳动物STC 1在调节免疫/炎症反应中的作用。
In macrophages, changes in intracellular calcium have been associated with activation of cellular processes that regulate cell adhesion and motility and are important for the response of macrophages to antigenic stimuli. The mammalian counterpart of the fish calcium-regulating hormone stanniocalcin-1 (STC1) is expressed in multiple organs including the thymus and spleen, and hence, we hypothesized that it may have a role in modulating the immune/inflammatory response. Using murine macrophage-like (RAW264.7) and human monoblast-ike (U937) cells to study chemotaxis in vitro, we found that STC1 attenuated chemokinesis and diminished the chemotactic response to monocyte chemotactic protein-1 (MCP-1) and stromal cell-derived factor-1alpha. Consistent with these findings, STC1 blunted the rise in intracellular calcium following MCP-1 stimulation in RAW264.7 cells. In vivo studies suggested differential expression of STC1 in obstructed kidney and localization to macrophages. MCP-1 and STC1 transcripts were both upregulated following ureteric obstruction, suggesting a functional association between the two genes. Our data suggest a role for mammalian STC1 in modulating the immune/inflammatory response.