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

CHEN, M.-F., H.-I. CHEN, and C.J. JEN. Exercise Training Upregulates Macrophage MKP-1 and Affects Immune Responses in Mice. Med. Sci. Sports Exerc., Vol. 42, No. 12, pp. 2173-2179, 2010. 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-alpha (TNF-alpha) 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-alpha 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-alpha, 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.