Gene-inducing program of human dendritic cells in response to BCG cell-wall skeleton (CWS), which reflects adjuvancy required for tumor immunotherapy
Gene-inducing program of human dendritic cells in response to BCG cell-wall skeleton (CWS), which reflects adjuvancy required for tumor immunotherapy
复制标题
DOI：
10.1016/j.imlet.2004.12.002
复制
发表时间：
2005-05-15
影响因子：
4.4
通讯作者：
Seya, T
中科院分区：
文献类型：
--
作者：
Ishii, K;Kurita-Taniguchi, M;Seya, T
佐剂诱导树突状细胞（DC）中许多基因的表达，其促进有效的抗原呈递和细胞因子/趋化因子释放。Toll样受体（TLR）家族控制DC的佐剂活性已被公认。具有悠久历史的佐剂是水包油乳剂中的分枝杆菌，即弗氏完全佐剂。由于分枝杆菌中粘附性的活性中心是细胞壁骨架（CWS），我们使用卡介苗细胞壁骨架（BCG-CWS）通过基因芯片（TM）分析来测试DC成熟。我们鉴定了支持有效DC响应和输出的基因。大约有2000个基因被BCG CWS刺激上调。BCG-CWS-、肽聚糖（PGN）-和脂多糖（LPS）-刺激通常上调一些基因簇，包括炎性细胞因子（TNF、IL 1 α、IL 1 β、IL 6、IL 12 p40、IL 23 p19等）的基因，趋化因子（CCL 20、IL 8等），细胞粘附分子（ICAM-1等），糖尿病相关蛋白（GADD 45 B、BCL 2A 1等），代谢酶（PTGS 2、SOD 2等）和其他蛋白质（EHD 1、TNFAIP 6等）。LPS刺激，而不是BCG-CWS-或PGN-刺激，上调干扰素诱导的抗病毒蛋白，包括IFIT 1，IFIT 2，IFIT 4，CXCL 10，ISG 15，OASL，IFITM 1和MX 1。我们还发现BCG-CWS-或PGN-刺激上调CXCL 5、MMP 1等。我们讨论了它们与TLR和最近发现的TLR接头的相关性质。(c)2004 Elsevier B. V.保留所有权利。
Adjuvants induce the expression of a number of genes in dendritic cells (DCs), which facilitate effective antigen-presentation and cytokine/chemokine liberation. It has been accepted that the toll-like receptor (TLR) family governs the adjuvant activity in DCs. An adjuvant with a long history is mycobacteria in an oil-in-water emulsion, namely Freund's complete adjuvant. Since the active center for the adjuvancy in mycobacteria is the cell-wall skeleton (CWS), we used the bacillus Calmette-Guerin cell-wall skeleton (BCG-CWS) to test DC maturation by GeneChip (TM) analysis. We identified the genes supporting an efficient DC response and output. Approximately 2000 genes were up-regulated by BCG-CWS stimulation. BCG-CWS-, peptidoglycan (PGN)- and lipopolysaccharide (LPS)-stimulation generally up-regulated some gene clusters including genes for inflammatory cytokines (TNF, IL1 alpha, IL1 beta, IL6, IL12 p40, IL23 p19, etc.), chemokines (CCL20, IL8, etc.), cell adhesion molecules (ICAM-1, etc.), apoptosis-related proteins (GADD45B, BCL2A1, etc.), metabolic enzymes (PTGS2, SOD2, etc.) and miscellaneous proteins (EHD1, TNFAIP6, etc.). LPS-stimulation, but not BCG-CWS- or PGN-stimulation, up-regulated the interferon-inducible antiviral proteins, including IFIT1, IFIT2, IFIT4, CXCL10, ISG15, OASL, IFITM1 and MX1. We also found that the BCG-CWS-or PGN-stimulation up-regulated CXCL5, MMP1, etc, We discussed their properties in association with TLRs and recently discovered TLR adapters. (c) 2004 Elsevier B.V. All rights reserved.