Pediatric Exercise Research Center, Department of Pediatrics, University of California, Irvine, Irvine, California 92697-4094, USA.
J Appl Physiol (1985). 2013 Mar 1;114(5):628-36. doi: 10.1152/japplphysiol.01341.2012. Epub 2013 Jan 3.
Natural killers (NK) cells are unique innate immune cells that increase up to fivefold in the circulating blood with brief exercise and are known to play a key role in first-response defense against pathogens and cancer immunosurveillance. Whether exercise alters NK cell gene and microRNA (miRNA) expression is not known. Thirteen healthy men (20-29 yr old) performed ten 2-min bouts of cycle ergometer exercise at a constant work equivalent to an average of 77% of maximum O2 consumption interspersed with 1-min rest. Blood was drawn before and immediately after the exercise challenge. NK cells were isolated from peripheral blood mononuclear cells using a negative magnetic cell separation method. We used Affymetrix U133+2.0 arrays for gene expression and Agilent Human miRNA V2 Microarray for miRNAs. A stringent statistical approach (false discovery rate < 0.05) was used to determine that exercise significantly altered the expression of 986 genes and 23 miRNAs. Using in silico analysis, we found exercise-related gene pathways where there was a high likelihood of gene-miRNA interactions. These pathways were predominantly associated with cancer and cell communication, including p53 signaling pathway, melanoma, glioma, prostate cancer, adherens junction, and focal adhesion. These data support the hypothesis that exercise affects the gene and miRNA expression pattern in the population of NK cells in the circulation and suggest mechanisms through which physical activity could alter health through the innate immune system.
自然杀伤 (NK) 细胞是独特的先天免疫细胞,在短暂运动后其循环血液中的数量会增加五倍,已知其在针对病原体的初次防御和癌症免疫监视中发挥关键作用。目前尚不清楚运动是否会改变 NK 细胞的基因和 microRNA (miRNA) 表达。13 名健康男性(20-29 岁)进行了 10 次 2 分钟的固定自行车运动,每次运动的工作量相当于平均 77%的最大耗氧量,其间穿插 1 分钟的休息时间。在运动挑战之前和之后立即抽取血液。使用负磁细胞分离法从外周血单核细胞中分离 NK 细胞。我们使用 Affymetrix U133+2.0 阵列进行基因表达分析,使用 Agilent Human miRNA V2 Microarray 进行 miRNA 分析。使用严格的统计方法(错误发现率 < 0.05)确定运动显著改变了 986 个基因和 23 个 miRNA 的表达。通过计算分析,我们发现运动相关的基因途径中存在高度可能的基因-miRNA 相互作用。这些途径主要与癌症和细胞通讯有关,包括 p53 信号通路、黑色素瘤、神经胶质瘤、前列腺癌、黏附连接和焦点黏附。这些数据支持运动影响循环 NK 细胞群体中基因和 miRNA 表达模式的假设,并表明通过先天免疫系统改变健康的可能机制。