Angiocidin promotes pro-inflammatory cytokine production and antigen presentation in multiple sclerosis
Angiocidin promotes pro-inflammatory cytokine production and antigen presentation in multiple sclerosis
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DOI：
10.1016/j.jneuroim.2007.11.003
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发表时间：
2008-02-01
影响因子：
3.3
通讯作者：
Tuszynski, George
中科院分区：
文献类型：
--
作者：
Kremlev, Sergey G.;Gaurnier-Hausser, Anita L.;Tuszynski, George
血管杀虫素最初被认为是体内血管生成和肿瘤生长的有效抑制剂。除了参与肿瘤发生的调节，最近的研究表明，血管杀虫素也可能在免疫系统调节中发挥重要作用。本报告描述了血管杀虫素在多发性硬化症（MS）中的表达和潜在功能，多发性硬化症是一种严重的脱髓鞘、炎症和中枢神经系统（CNS）自身免疫性疾病。我们证实了血管杀虫素和白介素-7 （IL-7）在MS患者的脑病变中过度表达。抗血管毒素处理的单核细胞、外周血T细胞和原代星形胶质细胞分泌各种细胞因子和趋化因子，包括IL-6、IL-7、GM-CSF和MCP-1。在细胞培养中加入重组抗血管毒素能够促进单核细胞向巨噬细胞样细胞分化，诱导MHC I类和II类。激活CD4（+）和CD8(+) T淋巴细胞。与这些发现一致的是，抗血管杀虫素诱导单核吞噬细胞迁移和粘附，并增加抗原特异性T细胞对自体单核吞噬细胞呈递的髓鞘碱性蛋白肽的IL-2反应。此外，我们检测了STAT3在抗血管毒素刺激的单核吞噬细胞、T细胞和原代星形胶质细胞中的表达。我们发现，血管杀菌素显著刺激这些细胞群中STAT3的表达。因此，血管杀菌素似乎在ms临床过程中的免疫反应调节中发挥了以前未被认识到的潜在重要作用(C) 2007 Elsevier B.V.。
Angiocidin was originally identified as a potent inhibitor of angiogenesis and tumor growth in vivo. In addition to its involvement in the regulation of carcinogenesis, recent studies indicate that angiocidin may also play a significant role in immune system modulation. This report describes the expression and potential function of angiocidin in multiple sclerosis (MS), a severe demyelinating, inflammatory and autoimmune disease of the central nervous system (CNS). We demonstrated that angiocidin and interleukin-7 (IL-7) are over-expressed in brain lesions of MS patients. Angiocidin-treated monocytes, peripheral blood T cells and primary astrocytes secreted various cytokines and chemokines including, IL-6, IL-7, GM-CSF, and MCP-1. Addition of recombinant angiocidin to cell cultures was able to promote differentiation of monocytes into a macrophage-like cell, induce MHC class I and class II. gene expression and activate CD4(+) and CD8(+) T lymphocytes. Consistent with these findings, angiocidin induced mononuclear phagocyte migration and adhesion as well as increased the IL-2 response by antigen-specific T cells to myelin basic protein peptide presented to them by autologous mononuclear phagocytes. Furthermore, we examined STAT3 expression in angiocidin stimulated mononuclear phagocytes, T cells, and primary astrocytes. We found that angiocidin markedly stimulates STAT3 expression in these cell populations. Angiocidin, therefore appears to play a previously unappreciated and potentially important role in the regulation of immune response during the clinical course of MS. (C) 2007 Elsevier B.V. All rights reserved.