IL-10 stimulatory effects on human NK cells explored by gene profile analysis

被引:85
作者
Mocellin, S [1 ]
Panelli, M
Wang, E
Rossi, CR
Pilati, P
Nitti, D
Lise, M
Marincola, FM
机构
[1] Univ Padua, Dept Oncol & Surg Sci, I-35128 Padua, Italy
[2] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA
关键词
human NK cell; IL-10; gene profile;
D O I
10.1038/sj.gene.6364135
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The molecular mechanisms underlying the increase of natural killer (NK) cell anticancer activity mediated by interleukin (IL)-10 have not been elucidated. The aim of this study was to identify potential molecular mediators of IL-10 stimulatory effects by exploring the NK cell gene display induced by this cytokine. Gene profile was determined by high-throughput cDNA microarray and quantitative real-time PCR. In vitro, NK cells resting or conditioned with IL-10 were tested for cytotoxicity, migration and proliferation. IL-10 enhanced mRNA levels of cell activation/cytotoxicity- related genes (eg secretogranin, TIA-1, HMG-1, interferon-inducible genes) not upregulated by IL-2. In line with these findings, IL-10 increased NK cell in vitro cytotoxicity against Daudi cells. Unlike IL-2, IL-10 did not show any significant effect on NK cell in vitro proliferation and migration. However, gene profile analysis showed that IL-10 increased the expression of cell migration-related genes ( eg L-selectin, vascular endothelium growth factor receptor-1, plasminogen activator, tissue; formyl peptide receptor, lipoxin A4 receptor), which might support a stimulatory effect not evident with the in vitro functional assay. Overall, gene profiling allowed us to formulate new hypotheses regarding the molecular pathways underlying the stimulatory effects of IL-10 on NK cells, supporting further investigation aimed at defining its role in cancer immune rejection.
引用
收藏
页码:621 / 630
页数:10
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