Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults

Abstract

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.

Figures

Fig. 1.

An intersecting analysis of the specific natural killer (NK) microRNAs and genes whose expression was significantly altered by exercise and genes whose expression was also significantly altered by exercise. This approach identified six significant pathways and provided direction for further investigation of how microRNAs altered by exercise regulate NK cells function.

Fig. 2.

Effect of brief exercise on circulating interleukin (IL)-2 and IL-15 in the sample population. The figure shows individual responses before (Pre) and after (Post) the exercise bout. There was a significant increase in IL-15 but not in IL-2 (P = 0.0001 using paired t-test).