CXCR3 and CCR5 ligands in rheumatoid arthritis synovium
CXCR3 and CCR5 ligands in rheumatoid arthritis synovium
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DOI：
10.1006/clim.2000.4957
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发表时间：
2001-01-01
影响因子：
8.6
通讯作者：
Whichard, LP
中科院分区：
文献类型：
--
作者：
Patel, DD;Zachariah, JP;Whichard, LP
类风湿关节炎（RA）的发病机制可能是由Th 1型T细胞介导的。由于趋化因子受体CXCR 3和CCR 5优先在Th 1细胞上表达，我们测试了几种趋化因子的表达和调节，包括那些通过CXCR 3传递信号的趋化因子（10 kDa的干扰素-γ-诱导蛋白，IP-10，CXCL 10;和由干扰素-γ-诱导的单核因子，Mig，CXCL 9）和CCR 5（巨噬细胞炎性蛋白（Mip）-1 α，CCL 3;和Mip-1 β，CCL 4）。IP-10的滑液（SF）蛋白水平（32.1 +/- 10.5 ng/ml），米格（15.0 +/- 6.4 ng/ml），Mip-1 β（0.7 +/- 0.3 ng/ml）和Mip-1 α（0.8 +/-0.1 ng/ml）分别为对照组SF的100、50、25和2倍（分别为P < 0.001、P <0.001、P <0.001和P < 0.02）。IP-10、Mig和Mip-1 β的组织水平在RA中显著高于OA（P < 0.01）。血清阳性RA患者的IP-10血清水平（3.1 +/-1.2 ng/ml）高于对照组（1.2 +/-0.2 ng/ml）（P < 0.02）。在RA中，IP-10、Mig、Mip-1 α和Mip-1 β从血液进入滑液有梯度。RA滑膜中高内皮微静脉周围的浸润T细胞和90 +/- 3%的SF CD 3（+）CD 4（+）T细胞表达CXCR 3，85 +/- 2%的SF CD 3（+）CD 4（+）T细胞表达CCR 5。趋化因子，包括IP-10、Mig、Mip-1 α和Mip-1 β，可能参与CCR 5（+）CXCR 3（+）T细胞向发炎滑膜的选择性募集。(C)北京大学出版社.
The pathogenesis of rheumatoid arthritis (RA) may be mediated by Th1-type T cells. Since chemokine receptors CXCR3 and CCR5 are preferentially expressed on Th1 cells, we tested the expression and regulation of several chemokines, including those that signal through CXCR3 (interferon-gamma -inducible protein of 10 kDa, IP-10, CXCL10; and monokine induced by interferon-gammay, Mig, CXCL9) and CCR5 (macrophage inflammatory protein (Mip)-1 alpha, CCL3; and Mip-1 beta, CCL4) in RA synovial fluids, synovial tissues, and blood. Synovial fluid (SF) protein levels of IP-10 (32.1 +/- 10.5 ng/ml), Mig (15.0 +/- 6.4 ng/ml), Mip-1 beta (0.7 +/- 0.3 ng/ml), and Mip-1 alpha (0.8 +/- 0.1 ng/ml) were 100-, 50-, 25-, and 2-fold elevated in RASF compared to control SF (P < 0.001, P < 0.001, P < 0.001, and P < 0.02, respectively). Tissue levels of IP-10, Mig, and Mip-1 beta were significantly higher in RA than in OA (P < 0.01). Serum levels of IP-10 (3.1 +/- 1.2 ng/ml) were higher in patients with seropositive RA compared to controls (1.2 +/- 0.2 ng/ml) (P < 0.02). There was a gradient of IP-10, Mig, Mip-1 alpha, and Mip-1 beta from the blood into the synovial fluid in RA. Infiltrating T cells around high endothelial venules in RA synovium and 90 +/- 3% of SF CD3(+)CD4(+) T cells expressed CXCR3, and 85 +/- 2% of SF CD3(+)CD4(+) T cells expressed CCR5. Chemokines, including IP-10, Mig, Mip-1 alpha, and Mip-1 beta, may participate in the selective recruitment of CCR5(+)CXCR3(+) T cells to the inflamed synovium. (C) 2000 Academic Press.