CXC chemokine receptor 4 expression and stromal cell-derived factor-1α-induced chemotaxis in CD4+ T lymphocytes are regulated by interleukin-4 andinterleukin-10
CXC chemokine receptor 4 expression and stromal cell-derived factor-1α-induced chemotaxis in CD4+ T lymphocytes are regulated by interleukin-4 andinterleukin-10
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DOI：
10.1046/j.1365-2567.2000.00954.x
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发表时间：
2000-03-01
期刊：
影响因子：
6.4
通讯作者：
Poulsen, LK
中科院分区：
文献类型：
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作者：
Jinquan, T;Quan, S;Poulsen, LK
我们报道了白细胞介素（IL）-4和IL-10可分别显著上调或下调CD 4（+）T淋巴细胞上CXC趋化因子受体4（CXCR 4）的表达。基质细胞衍生因子-1 α（SDF-1 α）诱导的CD 4（+）T淋巴细胞趋化性也受到IL-4和IL-10的相应调节。实时定量逆转录聚合酶链反应（RT-PCR）检测IL-4和IL-10分别上调或下调CD 4（+）T淋巴细胞CXCR 4 mRNA表达。Scatchard分析显示，CXCR 4的一种类型，在新鲜分离的CD 4（+）T淋巴细胞中，K-d约为6.3 nm，每个细胞约有70000个SDF-1 α结合位点，两种CXCR 4具有不同的亲和力（K-d1约为4.4 nm，K-d2约为14.6 nm），并且在IL-4刺激的CD 4（+）T淋巴细胞中，每个细胞总共约有130 000个SDF-1 α结合位点。IL-4和IL-10对CD 4（+）T淋巴细胞CXCR 4表达的调节可被选择性蛋白激酶抑制剂（staurosporine）或选择性cAMP和cGMP依赖性蛋白激酶抑制剂（H-8）阻断，表明这些细胞因子通过cAMP和cGMP信号通路调节CD 4（+）T淋巴细胞上的CXCR 4。环孢菌素A或离子霉素能够独立地改变CXCR 4表达并阻断IL-4和IL-10对CXCR 4表达的作用，这一事实表明IL-4和IL-10调节CD 4（+）T淋巴细胞上CXCR 4的能力与钙动员刺激无关。这些结果表明，IL-4和IL-10对CXCR 4-SDF-1受体-配体对的作用可能在与炎症过程有关的细胞因子/趋化因子环境中以及在人类免疫缺陷病毒（HIV）感染的进展中特别重要。
We report that interleukin (IL)-4 and IL-10 can significantly up- or down-regulate CXC chemokine receptor 4 (CXCR4) expression on CD4(+) T lymphocytes, respectively. Stromal cell-derived factor-1 alpha (SDF-1 alpha)-induced CD4(+) T-lymphocyte chemotaxis was also correspondingly regulated by IL-4 and IL-10. IL-4 and IL-10 up- or down-regulated CXCR4 mRNA expression in CD4(+) T lymphocytes, respectively, as detected by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Scatchard analysis revealed a type of CXCR4 with affinity (K-d approximate to 6.3 nm), and approximate to 70 000 SDF-1 alpha-binding sites per cell, among freshly isolated CD4(+) T lymphocytes, and two types of CXCR4 with different affinities (K-d1 approximate to 4.4 nm and K-d2 approximate to 14.6 nm), and a total of approximate to 130 000 SDF-1 alpha-binding sites per cell, among IL-4-stimulated CD4(+) T lymphocytes. The regulation of CXCR4 expression in CD4(+) T lymphocytes by IL-4 and IL-10 could be blocked by a selective inhibitor of protein kinase (staurosporine) or by a selective inhibitor of cAMP- and cGMP-dependent protein kinase (H-8), indicating that these cytokines regulate CXCR4 on CD4(+) T lymphocytes via both cAMP and cGMP signalling pathways. The fact that cyclosporin A or ionomycin were able to independently change the CXCR4 expression and block the effects of IL-4 and IL-10 on CXCR4 expression implied that the capacity of IL-4 and IL-10 to regulate CXCR4 on CD4(+) T lymphocytes is not linked to calcium-mobilization stimulation. These results indicate that the effects of IL-4 and IL-10 on the CXCR4-SDF-1 receptor-ligand pair may be of particular importance in the cytokine/chemokine environment concerning the inflammatory processes and in the progression of human immunodeficiency virus (HIV) infection.