Evidence for microRNA involvement in exercise-associated neutrophil gene expression changes.

Exercise leads to a rapid change in the profile of gene expression in circulating neutrophils. MicroRNAs (miRNAs) have been discovered to play important roles in immune function and often act to attenuate or silence gene translation. We hypothesized that miRNA expression in circulating neutrophils would be affected by brief exercise. Eleven healthy men (19-30 yr old) performed 10, 2-min bouts of cycle ergometer exercise interspersed with 1-min rest at a constant work equivalent to approximately 76% of maximal oxygen uptake (Vo(2 max)). We used the Agilent Human miRNA V2 Microarray. A conservative statistical approach was used to determine that exercise significantly altered 38 miRNAs (20 had lower expression). Using RT-PCR, we verified the expression level changes from before to after exercise of seven miRNAs. In silico analysis showed that collectively 36 miRNAs potentially targeted 4,724 genes (2 of the miRNAs had no apparent gene targets). Moreover, when we compared the gene expression changes (n = 458) in neutrophils that have been altered by exercise, as previously reported, with the miRNAs altered by exercise, we identified three pathways, Ubiquitin-mediated proteolysis, Jak-STAT signaling pathway, and Hedgehog signaling pathway, in which an interaction of miRNA and gene expression was plausible. Each of these pathways is known to play a role in key mechanisms of inflammation. Brief exercise alters miRNA profile in circulating neutrophils in humans. These data support the hypothesis that exercise-associated changes in neutrophil miRNA expression play a role in neutrophil gene expression in response to physical activity.