Expression of chemokine and receptors in Lewis rats with experimental autoimmune anterior uveitis
Expression of chemokine and receptors in Lewis rats with experimental autoimmune anterior uveitis
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DOI：
10.1016/j.exer.2004.02.006
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发表时间：
2004-06-01
影响因子：
3.4
通讯作者：
Chen, MS
中科院分区：
文献类型：
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作者：
Fang, IM;Yang, CH;Chen, MS
本研究的目的是研究Lewis大鼠虹膜睫状体和腘淋巴结中某些趋化因子和趋化因子受体的顺序表达，从而确定它们在实验性自身免疫性前葡萄膜炎中的作用。通过腹膜内和左脚注射黑色素相关抗原诱导葡萄膜炎。对葡萄膜炎的临床严重程度进行评分。在规定的时间点，CC趋化因子（单核细胞趋化蛋白-1、巨噬细胞炎症蛋白-1和激活调节的正常T细胞表达和分泌）、CXC趋化因子（干扰素γ诱导蛋白-10、基质衍生因子-1和白细胞介素-8）和受体（CCR2、CCR3、CCR5、CXCR1、CXCR2、通过使用逆转录酶反应和随后的聚合酶链反应来半定量 CXCR3 和 CXCR4) mRNA 表达。通过酶联免疫吸附测定法测定房水中表达和分泌的巨噬细胞炎症蛋白-1和激活调节正常T细胞的浓度。单核细胞趋化蛋白-1、巨噬细胞炎症蛋白-1和干扰素γ诱导蛋白-10的水平在临床发病前开始升高；这些可能参与了炎症细胞的最初募集。然而，激活后调节的正常 T 细胞 mRNA 的水平在临床疾病发作的同时开始上升，表明这种趋化因子可能在葡萄膜炎的产生中发挥放大作用。随着同源受体CXCR4的增加，基质衍生因子1表现出早期和高水平的表达，表明基质衍生因子1在促进血管生成或吸引T细胞方面发挥作用。与其他趋化因子受体、白细胞介素8受体、CXCR1和CXCR2一样上调，但不能检测到与白细胞介素8增加一致的mRNA。这些发现表明，中性粒细胞趋化因子受体的下调可能会降低其对白细胞介素 8 的反应，从而导致虹膜睫状体中中性粒细胞的募集减少。此外，腘淋巴结趋化因子受体的表达早于虹膜体。这种表达顺序可能反映了T淋巴细胞成熟和分化的过程。通过免疫组织学方法在睫状上皮和浸润白细胞中检测到单核细胞趋化蛋白-1 蛋白。上述结果表明，作用于T细胞和单核细胞的趋化因子在实验性自身免疫性前葡萄膜炎的临床过程中依次上调，因此可能有助于急性前葡萄膜炎的发病机制。 (C) 2004 Elsevier Ltd. 保留所有权利。
The purpose of this study is to investigate the sequential expression of certain chemokines and chemokine receptors in the iris-ciliary body and popliteal lymph nodes of Lewis rats and, thus, to establish their roles in experimental autoimmune anterior uveitis. Uveitis was induced with the injection of melanin-associated antigen intraperitoneally and into the left foot. The clinical severity of the uveitis was scored. At defined time points, CC chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1, and regulated-upon-activation normal T-cell expressed and secreted), CXC chemokines (interferon gamma-inducible protein-10, stromal-derived factor-1, and interleukin-8), and receptor (CCR2, CCR3, CCR5, CXCR1, CXCR2, CXCR3, and CXCR4) mRNA expression were semiquantified by using a reverse-transcriptase reaction followed by polymerase chain reaction. The concentrations of macrophage inflammatory protein-1 and regulated-upon-activation normal T-cell expressed and secreted in aqueous humor were determined by means of enzyme-linked immunosorbent assay. Levels of monocyte chemoattractant protein-1, macrophage inflammatory protein-1 and interferon gamma-inducible protein-10 started increasing before the clinical onset of disease; these might have been involved in the initial recruitment of inflammatory cells. The level of regulated-upon-activation normal T-cell mRNA, however, started rising concurrently with the onset of clinical disease, suggesting that this chemokine may exert amplifying role in generating uveitis. Stromal-derived factor-1 exhibited an early and high level of expression with the increase of cognate receptor, CXCR4, indicating that stromal-derived factor-1 plays a role in either promoting angiogenesis or attracting for T-cells. Instead of upregulation like other chemokine receptors, interleukin-8 receptors, CXCR1 and CXCR2, mRNA could not be detected in accord with the increase of interleukin-8. These findings appeared that downregulation of chemokine receptors on neutrophils may make themselves less respond to interleukin-8 and subsequently lead to decreased recruitment of neutrophils into the iris-ciliary body. In addition, the expression of chemokine receptors in popliteal lymph nodes were earlier than those in the irisciliary body. This sequence of expression may reflect the process of T lymphocytes maturation and differentiation. Monocyte chemoattractant protein-1 protein was immunohistologically detected in the ciliary epithelium and infiltrating leukocytes. The above results suggest that chemokines, which act on T cells and monocytes, are sequentially upregulated during the clinical course of experimental autoimmune anterior uveitis, and thus, may contribute to the pathogenesis of acute anterior uveitis. (C) 2004 Elsevier Ltd. All rights reserved.