ABSTRACT
Three-week exercise training decreased the steady state level of beta(2)-adrenergic receptor (beta(2)AR) mRNA in peritoneal macrophages from BALB/c mice. When peritoneal macrophages from both exercise-trained and sedentary control mice were stimulated with lipopolysaccharide (LPS), interleukin (IL)-12 mRNA and protein expression was markedly higher in trained mice than in control mice. To determine whether enhanced production of IL-12 was associated with decreased expression of beta(2)AR, we transfected the macrophage cell line, RAW264, with a eukaryotic expression vector containing beta(2)ar cDNA, establishing a cell line overexpressing beta(2)AR (RAWar). Following LPS stimulation, IL-12 mRNA and protein expression was significantly lower in RAWar cells than in RAW264 cells transfected with vector alone (RAWvec). Furthermore, when the expression of transfected beta(2)AR in RAWar cells was down-regulated by a tetracycline repressor-regulated mammalian expression system, expression of IL-12 mRNA and protein following LPS stimulation tended to return to the levels in RAWvec cells. These findings indicate that macrophage production of IL-12 following LPS stimulation is regulated by the expression level of beta(2)AR, suggesting that the down-regulation of beta(2)AR expression associated with exercise training improves IL-12-induced type 1 helper T cell-mediated immune responses.
Subject(s)
Down-Regulation/genetics , Interleukin-12/genetics , Lipopolysaccharides/pharmacology , Macrophages, Peritoneal/physiology , Physical Conditioning, Animal , Receptors, Adrenergic, beta-2/genetics , Animals , Cell Line , DNA, Complementary/genetics , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/immunology , Male , Mice , Mice, Inbred BALB C , RNA, Messenger/geneticsABSTRACT
Calcineurin, a calcium-regulated protein phosphatase, activates gene expression specific to slow muscle fibers by dephosphorylating a family of the nuclear factor of activated T cells (NFAT), which cooperates with myocyte enhancer factor-2 (MEF2) and AP-1. However, it remains unknown how acute exercise influences this signaling pathway and leads to the development of slow muscle fibers. In the present study, we investigated the effect of moderate acute exercise on mRNA expression of genes in the calcineurin signaling pathway in human skeletal muscle. Five healthy volunteers underwent 1 h bicycle ergometer at 50%VO2max, and vastus lateralis muscle biopsies were collected before and after exercise. Four hours after exercise, alterations in mRNA expression of NFAT 1-3 were observed with a wide variety among subjects, while c-fos mRNA was significantly induced in all subjects. By contrast, the expression of calcineurin, MEF2, and myocyte-enriched calcineurin-interacting protein 1 (MCIP1) remained unchanged. These results suggest that even moderate acute exercise may change mRNA expression of genes in the calcineurin-signaling pathway.
