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Exercise Training Upregulates Macrophage MKP-1 and Affects Immune Responses in Mice


Medicine & Science in Sports & Exercise: December 2010 - Volume 42 - Issue 12 - p 2173-2179
doi: 10.1249/MSS.0b013e3181e2158d
Basic Sciences

Purpose: Currently, it is unclear how chronic exercise affects immunity. Mitogen-activated protein kinase (MAPK) mediates the production of proinflammatory cytokines, whereas MAPK phosphatase-1 (MKP-1) plays an essential role in intracellular homeostasis by negatively regulating macrophage MAPK activation. We hypothesized that chronic exercise might upregulate macrophage MKP-1 and thus prevent excessive inflammatory responses.

Methods: To verify this hypothesis, we compared the basal immune status and lipopolysaccharide (LPS)-evoked immune responses between sedentary and 8-wk treadmill exercise-trained male C57BL/6 mice.

Results: Although the basal levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were undetectable in the serum of both groups, the exercised mice showed the following immune adaptations in vivo: (i) higher basal MKP-1 mRNA level in peritoneal macrophages, (ii) lower basal p38 MAPK activity and enhanced MKP-1 immunostaining in macrophages, and (iii) lower serum levels of IL-6 and TNF-α and less leukocyte infiltration into peritoneal cavity after systemic administration of LPS when compared with sedentary controls. In addition, when peritoneal macrophages isolated from exercised mice were exposed to LPS in vitro, they showed (i) accelerated MKP-1 protein expression, (ii) reduced p38 MAPK activity, and (iii) reduced cytokine secretion of IL-6, TNF-α, and monocyte chemotactic protein-1. Finally, 2 months of deconditioning completely reversed the exercise-enhanced basal MKP-1 immunostaining in macrophages and the exercise-suppressed cytokine secretion under LPS-evoked conditions.

Conclusions: Exercise training upregulated basal macrophage MKP-1 expression, accelerated LPS-evoked MKP-1 up-regulation, and affected LPS-evoked immune responses in mice.

1Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, TAIWAN; and 2Department of Physiology, National Cheng Kung University Medical College, Tainan, TAIWAN

Address for correspondence: Chauying J. Jen, Ph.D., Department of Physiology, National Cheng Kung, University Medical College, Tainan, 701 Taiwan; E-mail:

Submitted for publication December 2009.

Accepted for publication April 2010.

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©2010The American College of Sports Medicine