Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells
Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells
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DOI：
10.1172/jci6685
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发表时间：
1999-10-01
影响因子：
15.9
通讯作者：
Westwick, J
中科院分区：
文献类型：
--
作者：
Jordan, NJ;Kolios, G;Westwick, J
除了作为白细胞迁移和激活调节剂的作用外，趋化因子及其受体还在血管生成、生长调节和 HIV-1 发病机制中发挥作用，这些作用涉及趋化因子对非造血细胞的作用。为了确定趋化因子受体是否在人结肠上皮中表达，通过 RT-PCR 检查 HT-29 细胞中淋巴趋化素、fractalkine、CCR1-10 和 CXCR1-5 趋化因子受体的表达。唯一一致检测到的受体是 CXCR4 (融合蛋白/LESTR)，尽管 HT-29 细胞不表达其配体基质细胞衍生因子 (SDF-1 α) 的 mRNA。使用抗CXCR4抗体的流式细胞术分析表明，CXCR4蛋白在大约一半的HT-29细胞的表面上表达。正常和发炎的人类结肠粘膜活检组织的免疫组织化学显示，CXCR4也在体内结肠上皮细胞中表达。 SDF-1 α 和其他 CC 和 CXC 趋化因子的 mRNA 存在于正常结肠活检中。 HT-29 细胞中的 CXCR4 受体在功能上耦合，如 [Ca2+](i) 升高所证明的，这种升高是响应 25 nM SDF-1 α 和 SDF-1 α 诱导的 ICAM-1 mRNA 上调而发生的。丁酸钠下调 CXCR4 表达并诱导 HT-29 细胞分化，表明 CXCR4 在结肠上皮的维持和更新中发挥作用。这种受体也作为艾滋病毒的辅助受体，可能介导病毒。结肠上皮细胞感染。
In addition to their role as regulators of leukocyte migration and activation, chemokines and their receptors also function in angiogenesis, growth regulation, and HIV-1 pathogenesis - effects that involve the action of chemokines on nonhematopoietic cells. To determine whether chemokine receptors are expressed in human colonic epithelium, HT-29 cells were examined by RT-PCR for the expression of the chemokine receptors for lymphotactin, fractalkine, CCR1-10, and CXCR1-5. The only receptor consistently detected was CXCR4 (fusin/LESTR), although HT-29 cells did not express mRNA for its ligand, stromal cell-derived factor (SDF-1 alpha). Flow cytometric analysis with anti-CXCR4 antibody indicated that the CXCR4 protein was expressed on the surface of roughly half of HT-29 cells. CXCR4 was also expressed in colonic epithelial cells in vivo as shown by immunohistochemistry on biopsies from normal and inflamed human colonic mucosa. The mRNA for SDF-1 alpha and other CC and CXC chemokines was present in normal colonic biopsies. The CXCR4 receptor in HT-29 cells was functionally coupled, as demonstrated by the elevation in [Ca2+](i), which occurred in response to 25 nM SDF-1 alpha and by the SDF-1 alpha-induced upregulation of ICAM-1 mRNA. Sodium butyrate downregulated CXCR4 expression and induced differentiation of HT-29 cells, suggesting a role for CXCR4 in maintenance and renewal of the colonic epithelium. This receptor, which also serves as a coreceptor for HIV, may mediate viral. infection of colonic epithelial cells.