Exercise training upregulates macrophage MKP-1 and affects immune responses in mice.
OBJECTIVE
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.
Chen
Mei-Feng
MF
Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.
Chen
Hsiun-Ing
HI
Jen
Chauying J
CJ
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005080:Exercise Test; D007107:Immune System / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010805:Physical Conditioning, Animal / Q000502:physiology*; D015854:Up-Regulation
D016207:Cytokines; D008070:Lipopolysaccharides; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse