Submitted on November 29, 2007
Accepted on March 14, 2008
Inflammatory gene changes associated with the repeated bout effect
Monica J. Hubal1*, Trevor C Chen2, Paul D. Thompson3, and Priscilla M Clarkson4
1 Genetic Medicine, Children's National Medical Center, Washington, District of Columbia, United States; Exercise Science, University of Massachusetts, 110 Totman, Amherst, Massachusetts, 01003, United States
2 Department of Physical Education, National Chiayi University, Chiayi County, Taiwan - Republic of China
3 Cardiology, Hartford Hospital, Hartford, Connecticut, United States
4 Kinesiology, University of Massachusetts, Amherst, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: mhubal{at}cnmcresearch.org.
This study proposed that attenuated expression of inflammatory factors is an underlying mechanism driving the repeated bout effect (rapid adaptation to eccentric exercise). We investigated changes in mRNA levels and protein localization of inflammatory genes following two bouts of muscle lengthening exercise. Seven male subjects performed 2 bouts of lower body exercise (separated by 4 wks) in which one leg (ECC) performed 300 eccentric/concentric actions, and the contralateral leg (CON) performed 300 concentric actions only. Vastus lateralis biopsies were collected at 6h, and strength was assessed at baseline, and 0, 3 and 5d post-exercise. mRNA levels were measured via semi-quantitative RT-PCR for the following genes: CYR61, HSP40, HSP70, IL1R1, TCF8, ZFP36, CEBPD, and MCP-1. Muscle functional adaptation was demonstrated via attenuated strength loss (16% less; p=0.04) at 5d post-bout 2 as compared to bout 1 in the ECC leg. mRNA expression of three of the eight genes tested was significantly elevated in ECC from bout 1 to bout 2: ZFP36 (+3.9-fold), CEBPD (+2.3-fold) and MCP-1 (+2.6-fold), while all eight mRNA levels were unaffected by bout in the CON leg. Immunohistochemistry further localized the protein of one of the elevated factors (MCP-1) within the tissue. MCP-1 co-localized with resident macrophage and satellite cell populations, suggesting that alterations in cytokine signaling between these cell populations may play a role in muscle adaptation to exercise. Contrary to our hypothesis, several inflammatory genes were transcriptionally upregulated (rather than attenuated) after a repeated exercise bout, potentially indicating a role for these genes in the adaptation process.
