Increased levels of chemokine receptor CXCR3 and chemokines IP-10 and MIG in patients with primary biliary cirrhosis and their first degree relatives
Increased levels of chemokine receptor CXCR3 and chemokines IP-10 and MIG in patients with primary biliary cirrhosis and their first degree relatives
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DOI：
10.1016/j.jaut.2005.08.009
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发表时间：
2005-09-01
影响因子：
12.8
通讯作者：
Gershwin, ME
中科院分区：
文献类型：
--
作者：
Chuang, YH;Lian, ZX;Gershwin, ME
浸润性记忆T细胞在原发性胆汁性肝硬化（PBC）的胆道破坏中起重要作用，并且炎性趋化因子通过与T细胞趋化因子受体的相互作用控制淋巴细胞运输。在本研究中，我们检测了105名受试者，包括53名PBC患者，26名一级亲属和26名健康对照者的血浆趋化因子γ干扰素诱导蛋白-10（IP-10）和γ干扰素（IFN-γ）诱导的单核细胞因子水平，并研究了CXCR 3趋化因子受体的表达。有趣的是，PBC中的血浆IP-10和IP 10水平与对照相比显著增加，并且似乎随着疾病进展而增加。免疫组化结果显示，PBC汇管区内IP-10和P450表达明显。此外，外周血中CXCR 3表达细胞的频率在PBC中也显著更高，并且在患病肝脏的汇管区中也发现了CXCR 3阳性细胞，主要在CD 4（+）细胞上。最后，PBC患者的女儿和姐妹篇也表现出IP-10和IFN-γ的血浆水平升高，但相反，表现出表达CXCR 3（+）的外周血淋巴细胞的正常频率。我们的数据暗示了特异性趋化因子-趋化因子受体相互作用在PBC发病机制中的作用，也突出了家族性风险因素。(c)2005爱思唯尔有限公司保留所有权利。
Infiltrating memory T cells play an important role in the destruction of the biliary tract in primary biliary cirrhosis (PBC) and inflammatory chemokines control lymphocyte traffic through their interactions with T cell chemokine receptors. In the present study, we measured plasma levels of chemokines interferon-gamma-inducible protein-10 (IP-10) and monokine induced by gamma interferon (MIG), and also studied the expression of CXCR3 chemokine receptors in 105 subjects, including 53 patients with PBC, 26 first degree relatives and 26 healthy controls. Interestingly, plasma IP-10 and MIG levels in PBC were increased significantly compared to controls and appeared to increase with disease progression. By immunohistochemistry, IP-10 and MIG expressions were evident in the portal areas in PBC. Further, the frequency of CXCR3-expressing cells in peripheral blood was also significantly higher in PBC, and CXCR3-positive cells were also found in the portal areas of diseased livers, primarily on CD4(+) cells. Finally, (he daughters and sisters of PBC patients also demonstrated increased plasma levels of IP-10 and MIG, but, in contrast, displayed normal frequency of CXCR3(+) expressing peripheral blood lymphocytes. Our data imply a role for specific chemokine-chemokine receptor interactions in the pathogenesis of PBC and also highlight the familial risk factor. (c) 2005 Elsevier Ltd. All rights reserved.