Glial and neuronal cells express functional chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor 1

Glial and neuronal cells express functional chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor 1
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DOI:
10.1046/j.1471-4159.1999.0732348.x
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发表时间:
1999-12-01
影响因子:
4.7
通讯作者:
Schettini, G
Schettini, G
中科院分区:
医学2区
文献类型:
--
作者:
Bajetto, A;Bonavia, R;Schettini, G

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趋化因子是一个蛋白质家族,其通过与其靶标表面上的特异性受体相互作用来化学吸引并激活细胞。趋化因子基质细胞衍生因子1(SDF 1)与七跨膜G蛋白偶联的CXGR 4受体结合,并调节细胞迁移、分化和增殖。据报道,CXCR 4和SDF 1在包括脑在内的多种组织中表达。在这里,我们表明,SDF 1和CXCR 4表达在培养的皮质I型大鼠星形胶质细胞,皮质神经元和小脑颗粒细胞。在皮质星形胶质细胞中,长时间的脂多糖治疗诱导SDF 1表达的增加和CXGR 4的下调,而佛波醇酯治疗不影响SDF 1的表达和下调CXCR 4受体的表达。我们还证明了人SDF 1 α(hSDF 1 α)的能力,以增加培养的星形胶质细胞和皮层神经元的细胞内钙水平,而在相同的条件下,小脑颗粒细胞没有修改其细胞内钙浓度。此外,在皮质星形胶质细胞中,hSDF 1 α与HIV-1衣壳糖蛋白gp 120的同时处理抑制了毛喉素处理诱导的环AMP形成。
Chemokines are a family of proteins that chemoattract and activate cells by interacting with specific receptors on the surface of their targets. The chemokine stromal cell-derived factor 1, (SDF1), binds to the seven-transmembrane G protein-coupled CXGR4 receptor and acts to modulate cell migration, differentiation, and proliferation, CXCR4 and SDF1 are reported to be expressed in various tissues including brain. Here we show that SDF1 and CXCR4 are expressed in cultured cortical type I rat astrocytes, cortical neurons, and cerebellar granule cells. In cortical astrocytes, prolonged treatment with lipopolysaccharide induced an increase of SDF1 expression and a down-regulation of CXGR4, whereas treatment with phorbol esters did not affect SDF1 expression and down-modulated CXCR4 receptor expression. We also demonstrated the ability of human SDF1 alpha (hSDF1 alpha) to increase the intracellular calcium level in cultured astrocytes and cortical neurons, whereas in the same conditions, cerebellar granule cells did not modify their intracellular calcium concentration. Furthermore, in cortical astrocytes, the simultaneous treatment of hSDF1 alpha with the HIV-1 capside glycoprotein gp120 inhibits the cyclic AMP formation induced by forskolin treatment.