Down-regulation of β2-adrenergic receptor expression by exercise training increases IL-12 production by macrophages following LPS stimulation
Down-regulation of β2-adrenergic receptor expression by exercise training increases IL-12 production by macrophages following LPS stimulation
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DOI：
10.1016/j.bbrc.2004.08.050
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发表时间：
2004-09-24
影响因子：
3.1
通讯作者：
Ohno, H
中科院分区：
文献类型：
--
作者：
Itoh, CE;Kizaki, T;Ohno, H
三周的运动训练降低了BALB/c小鼠腹腔巨噬细胞β(2)-肾上腺素能受体（β (2)AR） mRNA的稳态水平。当运动训练小鼠和静止对照组小鼠的腹腔巨噬细胞受到脂多糖（LPS）刺激时，训练小鼠的白细胞介素(IL)-12 mRNA和蛋白表达明显高于对照组小鼠。为了确定IL-12的增强是否与β (2)AR的表达降低相关，我们用含有β (2)AR cDNA的真核表达载体转染巨噬细胞系RAW264，建立了过表达β (2)AR的细胞系（RAWar）。LPS刺激后，RAWar细胞中IL-12 mRNA和蛋白的表达明显低于单独转染载体（RAWvec）的RAW264细胞。此外，当转染的β (2)AR在RAWar细胞中被四环素抑制因子调控的哺乳动物表达系统下调表达时，LPS刺激后IL-12 mRNA和蛋白的表达倾向于恢复到RAWvec细胞的水平。这些发现表明，LPS刺激后巨噬细胞IL-12的产生受到β (2)AR表达水平的调节，表明运动训练相关的β (2)AR表达下调可改善IL-12诱导的1型辅助性T细胞介导的免疫反应。(C) 2004爱思唯尔公司版权所有。
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. (C) 2004 Elsevier Inc. All rights reserved.