Allograft inflammatory factor-1 stimulates chemokine production and induces chemotaxis in human peripheral blood mononuclear cells

Allograft inflammatory factor-1 stimulates chemokine production and induces chemotaxis in human peripheral blood mononuclear cells
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DOI:
10.1016/j.bbrc.2014.04.106
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发表时间:
2014-06-06
影响因子:
3.1
通讯作者:
Kawahito, Yutaka
Kawahito, Yutaka
中科院分区:
生物学4区
文献类型:
--
作者:
Kadoya, Masatoshi;Yamamoto, Aihiro;Kawahito, Yutaka

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同种异体移植物炎性因子-1(AIF-1)在免疫炎性疾病如系统性硬化症、类风湿性关节炎和几种血管病中由巨噬细胞、成纤维细胞、内皮细胞和平滑肌细胞表达。然而,其分子功能尚未完全了解。在这项研究中,我们研究了基因表达谱和诱导单核细胞与重组人AIF(rhAIF-1)的趋化因子。采用高密度寡核苷酸芯片技术,比较rhAIF-1刺激的健康志愿者CD 14(+)外周血单个核细胞(CD 14(+)PBMCs)mRNA表达谱。我们证实了几种CC趋化因子如CCL 1、CCL 2、CCL 3、CCL 7和CCL 20的基因上调。接下来,使用ELISA,我们证实rhAIF-1促进CD 14(+)PBMC分泌CCL 3/MIP-1 α和IL-6,而仅分泌少量的CCL 1、CCL 2/MCP-1、CCL 7/MCP-3和CCL 20/MIP-3 α。来自rhAIF-1刺激的CD 14(+)PBMC的条件培养基导致PBMC迁移。这些发现表明,AIF-1,诱导趋化因子和增强单核细胞的趋化性,可能代表免疫炎症性疾病的治疗的分子靶点。(C)2014爱思唯尔公司All rights reserved.
Allograft inflammatory factor-1 (AIF-1) is expressed by macrophages, fibroblasts, endothelial cells and smooth muscle cells in immune-inflammatory disorders such as systemic sclerosis, rheumatoid arthritis and several vasculopathies. However, its molecular function is not fully understood. In this study, we examined gene expression profiles and induction of chemokines in monocytes treated with recombinant human AIF (rhAIF-1). Using the high-density oligonucleotide microarray technique, we compared mRNA expression profiles of rhAIF-1-stimulated CD14(+) peripheral blood mononuclear cells (CD14(+) PBMCs) derived from healthy volunteers. We demonstrated upregulation of genes for several CC chemokines such as CCL1, CCL2, CCL3, CCL7, and CCL20. Next, using ELISAs, we confirmed that rhAIF-1 promoted the secretion of CCL3/MIP-1 alpha and IL-6 by CD14(+) PBMCs, whereas only small amounts of CCL1, CCL2/MCP-1, CCL7/MCP-3 and CCL20/MIP-3 alpha were secreted. Conditioned media from rhAIF-1 stimulated CD14(+) PBMCs resulted in migration of PBMCs. These findings suggest that AIF-1, which induced chemokines and enhanced chemotaxis of monocytes, may represent a molecular target for the therapy of immune-inflammatory disorders. (C) 2014 Elsevier Inc. All rights reserved.