title: Down-regulation of beta2-adrenergic receptor expression by exercise training increases IL-12 production by macrophages following LPS stimulation.
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.
authors.affiliation: Department of Molecular Predictive Medicine and Sport Science, School of Medicine, Kyorin University, Mitaka, Tokyo 181-8611, Japan.
authors.forename: Choh-Ei
authors.initials: CE
authors.lastname: Itoh
authors.forename: Takako
authors.initials: T
authors.lastname: Kizaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hitomi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hanawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kamiya
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ookawara
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Izawa
authors.forename: Daizoh
authors.initials: D
authors.lastname: Saitoh
authors.forename: Shukoh
authors.initials: S
authors.lastname: Haga
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohno
mesh_terms: D000818:Animals; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D018664:Interleukin-12 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D018664:Interleukin-12