CXCR3 surface expression in human airway epithelial cells: cell cycle dependence and effect on cell proliferation
CXCR3 surface expression in human airway epithelial cells: cell cycle dependence and effect on cell proliferation
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DOI：
10.1152/ajplung.00430.2005
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发表时间：
2006-05-01
影响因子：
4.9
通讯作者：
Kelsen, SG
中科院分区：
文献类型：
--
作者：
Aksoy, MO;Yang, Y;Kelsen, SG
我们最近发现，人支气管上皮细胞（HBEC）组成型表达CXC趋化因子受体CXCR 3，当激活时，诱导定向细胞迁移。目前在HBEC中的研究检查了CXCR 3剪接变体CXCR 3-A和- B的相对表达、CXCR 3表达的细胞周期依赖性以及CXCR 3配体、干扰素-γ诱导的CXC趋化因子I-TAC/CXCL 11对DNA合成和细胞增殖的影响。实时定量RT-PCR检测正常HBEC（NHBEC）和HBEC系16-HBE中CXCR 3-A和CXCR 3- B mRNA表达。然而，在NHBEC和16-HBE中，CXCR 3-B mRNA分别是CXCR 3-A mRNA的39倍和6倍。虽然通过流式细胞术和免疫荧光显微镜评估的大多数HBEC（> 80%）含有细胞内CXCR 3，但只有少数（< 40%）在细胞表面表达。在后一个细胞亚群中，大多数（> 75%）处于细胞周期的S + G（2）/M期。用I-TAC刺激CXCR 3增强胸苷掺入和细胞增殖，并增加p38和ERK 1/2磷酸化。这些数据表明：1）人气道上皮细胞主要表达CXCR 3-B mRNA，2）CXCR 3的表面表达主要局限于细胞周期的S + G（2）/M期，3）CXCR 3的活化诱导DNA合成、细胞增殖和MAPK途径的活化。我们推测CXCR 3的激活在HBEC中发挥促有丝分裂作用，这在阻塞性气道疾病如哮喘和慢性阻塞性肺疾病的气道粘膜损伤过程中可能是重要的。
We recently demonstrated that human bronchial epithelial cells (HBEC) constitutively express the CXC chemokine receptor CXCR3, which when activated, induces directed cell migration. The present study in HBEC examined the relative expression of the CXCR3 splice variants CXCR3-A and - B, cell cycle dependence of CXCR3 expression, and the effects of the CXCR3 ligand, the interferon-gamma-inducible CXC chemokine I-TAC/CXCL11, on DNA synthesis and cell proliferation. Both CXCR3-A and - B mRNA, assessed by real-time RT-PCR, were expressed in normal HBEC (NHBEC) and the HBEC line 16-HBE. However, CXCR3-B mRNA was 39- and 6-fold greater than CXCR3-A mRNA in NHBEC and 16-HBE, respectively. Although most HBEC ( > 80%) assessed by flow cytometry and immunofluorescence microscopy contained intracellular CXCR3, only a minority ( < 40%) expressed it on the cell surface. In this latter subset of cells, most ( > 75%) were in the S + G(2)/M phases of the cell cycle. Stimulation of CXCR3 with I-TAC enhanced thymidine incorporation and cell proliferation and increased p38 and ERK1/2 phosphorylation. These data indicate that 1) human airway epithelial cells primarily express CXCR3-B mRNA, 2) surface expression of CXCR3 is largely confined to the S + G(2)/M phases of the cell cycle, and 3) activation of CXCR3 induces DNA synthesis, cell proliferation, and activation of MAPK pathways. We speculate that activation of CXCR3 exerts a mitogenic effect in HBEC, which may be important during airway mucosal injury in obstructive airway diseases such as asthma and chronic obstructive pulmonary disease.