Effects of exercise on gene expression in human peripheral blood mononuclear cells

• Published in: Journal of applied physiology (1985) Vol. 97; no. 4; pp. 1461 - 1469
• Main Authors: Connolly, Peter H, Caiozzo, Vincent J, Zaldivar, Frank, Nemet, Dan, Larson, Jennifer, Hung, She-pin, Heck, J. Denis, Hatfield, G. Wesley, Cooper, Dan M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01-10-2004; American Physiological Society
• Subjects: Adolescent; Adult; Biological and medical sciences; Blood Proteins - immunology; Cells; Cells, Cultured; Cytokines - blood; Cytokines - immunology; Exercise; Exercise - physiology; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation - immunology; Gene Expression Regulation - physiology; Human subjects; Humans; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - physiology; Male; Physical Exertion - physiology; Physical exercise; Human; Vertebrata; Blood cell; microarray; Mammalia; Mononuclear cell; Growth; Inflammation; Gene expression; Immunity
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00316.2004

Departments of 2 Pediatrics, 3 Orthopedics, 4 Microbiology and Molecular Genetics, and 5 Biological Chemistry, 1 Center for the Study of Health Effects of Exercise in Children, 7 Department Physiology and Biophysics, 6 Institute for Genomics and Bioinformatics, College of Medicine, University of California, Irvine, California 92697
Submitted 25 March 2004
; accepted in final form 6 June 2004
Exercise leads to increases in circulating levels of peripheral blood mononuclear cells (PBMCs) and to a simultaneous, seemingly paradoxical increase in both pro- and anti-inflammatory mediators. Whether this is paralleled by changes in gene expression within the circulating population of PBMCs is not fully understood. Fifteen healthy men (18–30 yr old) performed 30 min of constant work rate cycle ergometry ( 80% peak O 2 uptake). Blood samples were obtained preexercise (Pre), end-exercise (End-Ex), and 60 min into recovery (Recovery), and gene expression was measured using microarray analysis (Affymetrix GeneChips). Significant differential gene expression was defined with a posterior probability of differential expression of 0.99 and a Bayesian P value of 0.005. Significant changes were observed from Pre to End-Ex in 311 genes, from End-Ex to Recovery in 552 genes, and from Pre to Recovery in 293 genes. Pre to End-Ex upregulation of PBMC genes related to stress and inflammation [e.g., heat shock protein 70 (3.70-fold) and dual-specificity phosphatase-1 (4.45-fold)] was followed by a return of these genes to baseline by Recovery. The gene for interleukin-1 receptor antagonist (an anti-inflammatory mediator) increased between End-Ex and Recovery (1.52-fold). Chemokine genes associated with inflammatory diseases [macrophage inflammatory protein-1 (1.84-fold) and -1 (2.88-fold), and regulation-on-activation, normal T cell expressed and secreted (1.34-fold)] were upregulated but returned to baseline by Recovery. Exercise also upregulated growth and repair genes such as epiregulin (3.50-fold), platelet-derived growth factor (1.55-fold), and hypoxia-inducible factor-I (2.40-fold). A single bout of heavy exercise substantially alters PBMC gene expression characterized in many cases by a brisk activation and deactivation of genes associated with stress, inflammation, and tissue repair.
microarray; inflammation; growth; immunity
Address for reprint requests and other correspondence: D. M. Cooper, Center for the Study of Health Effects of Exercise in Children, Dept. of Pediatrics, Bldg. 25, 2nd Floor, 101 The City Dr., Orange, CA 92868 (E-mail: dcooper{at}uci.edu ).