Exhaustive exercise modifies different gene expression profiles and pathways in LPS-stimulated and un-stimulated whole blood cultures.

ABSTRACT

Exhaustive exercise can interfere with immunity, causing transient immunosuppression and infections/inflammation in athletes. We used microarray technology to analyze the gene expression profiles of whole blood in short time (1h) LPS-stimulated and un-stimulated cultures drawn before, 30min after, 3h after and 24h after a half-marathon run. Four male and 4 female athletes participated. Exercise induced differential expression of genes known to be involved in innate immunity/inflammatory response, metabolic response, DNA methylation, apoptosis and regulation of brain function. Several genes with prominent anti-inflammatory function were up-regulated in un-stimulated cultures, including ARG-1, SOCS3, DUSP-1, ORMs, IRAK3, and GJB6. Some of these genes were also strongly up-regulated in LPS-stimulated cultures (ARG-1, ORM2, and GJB6). Some genes were strongly up-regulated through exercise in LPS-stimulated cultures, but not in un-stimulated cultures (TNIP3, PLAU, and HIVEP1). There was also a row of genes, which were strongly down-regulated by exercise in LPS-stimulated cultures, notably IFN-ß1 and CXCL10. Exercise also significantly changed the expression of genes (OLIG2, TMEM106B) which are known to be related to brain function and expression of which has never been documented in peripheral blood. In summary, exhaustive exercise, in addition to modifying gene expression in un-stimulated cells, could also interfere with the early gene expression response to endotoxin. There was an anti-inflammatory bias of gene regulation by exercise, including genes involved in the negative regulation of TLRs signalling. The results of the present study demonstrate that some potentially important effects of exercise can only be detected in relation to pathogen stimulation.