Interleukin-1 (IL-1) inhibits growth of cytomegalovirus in human marrow stromal cells: Inhibition is reversed upon removal of IL-1

作     者：Iwata, M Vieira, J Byrne, M Horton, H Torok-Storb, B 

作者机构：Fred Hutchinson Canc Res Ctr Div Clin Res Seattle WA 98109 USA Genet Inst Cambridge MA 02140 USA 

出 版 物：《BLOOD》 (血液)

年 卷 期：1999年第94卷第2期

页      面：572-578页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NCI NIH HHS [CA18221] Funding Source: Medline NIDDK NIH HHS [DK51417, DK34431] Funding Source: Medline 

主　　题：骨髓细胞/药物作用 骨髓细胞/病毒学 细胞 培养的 巨细胞病毒/药物作用 巨细胞病毒/生长和发育 巨细胞病毒/生理学 基因 报告 绿色荧光蛋白质类 白细胞介素1/药理学 发光蛋白质类/生物合成 发光蛋白质类/遗传学 肽延伸因子1 肽延伸因子/遗传学 启动区(遗传学) 间质细胞/药物作用 间质细胞/病毒学 病毒复制/药物作用 人类 

摘      要：A Toledo strain cytomegalovirus (CMV) containing the gene for green fluorescent protein (GFP) under the control of elongation factor-1 promoter was used to study infection of human marrow stromal cells. Two stromal cell lines were used: HS-5, which secretes copious amounts of known cytokines and interleukins;and HS-27a, which does not secrete these activities. CMV growth and spread was monitored by counting green plaques and quantitating GFP intensity. Initial studies indicated that, whereas HS-5 and 27a have similar susceptibilities to infection, as evidenced by the same number of GFP(+) cells at day 2, HS-5 appears more resistant to growth and spread of CMV. Furthermore, conditioned media from HS-5 (HS-5 CM) inhibited CMV plaque formation in HS-27a, suggesting that factors secreted by HS-5 are responsible for limiting CMV growth. Neutralizing antibodies against interleukin-1 alpha (IL-1 alpha) and IL-1 beta completely blocked the ability of HS-5 CM to limit viral growth, suggesting that IL-1, which is known to be present in HS-5 CM, is responsible for this effect. When exogenous IL-1 beta was added to CMV-infected HS-27a, both the number of plaques and the intensity of GFP was significantly reduced in IL-1-treated HS 27a compared with untreated HS-27a (the number of plaques by day 18 was 20 +/- 3 v 151 +/- 12/well, respectively;GFP intensity was 535 +/- 165 v 6,516 +/- 652/well, respectively, in 4 separate experiments). At day 21, when IL-1 beta-treated, CMV-infected cultures were passaged and then cultured in the absence of IL-1 beta, CMV growth progressed with the kinetics of the original untreated culture, indicating that the IL-1 beta effect is reversible. Because HS-27a expresses the type I IL-l receptor, we speculate that the antiviral effects are mediated through IL-1-induced changes in cellular gene expression. DNA chip analysis of mRNA from IL-1 beta-treated and nontreated HS-27a cells has identified some candidate molecules, (C) 1999 by The American Soci