Department of Pharmacology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa 1757, Ishikari-Tobetsu 060-0293, Japan.
Department of Pharmacology, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa 1757, Ishikari-Tobetsu 060-0293, Japan.
Immunol Lett. 2014 Mar-Apr;158(1-2):109-15. doi: 10.1016/j.imlet.2013.12.015. Epub 2013 Dec 24.
In the present study, we examined the effect of stress-related catecholamines adrenaline and noradrenaline on macrophage expression of a new host defense factor REDD1 using murine macrophage cell line RAW264.7 and murine peritoneal macrophages. Short-term adrenaline exposure (15-60 min) upregulated REDD1 mRNA expression and its protein synthesis in macrophages. This adrenaline-induced REDD1 expression was completely blocked by β2-adrenoceptor selective antagonist ICI 118,551, whereas β2-adrenoceptor specific agonist salmeterol markedly enhanced REDD1 expression. Moreover, noradrenaline increased REDD1 mRNA expression at doses higher than the effective doses of adrenaline. The effect of adrenaline on REDD1 mRNA expression was mimicked by treatment with membrane-permeable cAMP analog 8-Br-cAMP. Thus, increased intracellular cAMP level resulting from β2-adrenoceptor stimulation appeared to be responsible for adrenaline-induced REDD1 mRNA expression. However, inhibiting protein kinase A (PKA) activity had no significant effect on REDD1 mRNA expression after β2-adrenoceptor stimulation. In addition, exchange protein activated by cAMP (Epac) agonist 8-CPT-20-O-Me-cAMP had no effect on REDD1 mRNA expression. Thus, β2-adrenoceptor-mediated increase in cAMP levels seems to induce REDD1 mRNA expression in macrophages through a PKA- and Epac-independent pathway.
在本研究中，我们使用小鼠巨噬细胞系 RAW264.7 和小鼠腹腔巨噬细胞研究了应激相关儿茶酚胺肾上腺素和去甲肾上腺素对巨噬细胞表达新的宿主防御因子 REDD1 的影响。短期肾上腺素暴露（15-60 分钟）可上调巨噬细胞中 REDD1 mRNA 的表达及其蛋白合成。这种肾上腺素诱导的 REDD1 表达被β2-肾上腺素受体选择性拮抗剂 ICI 118,551 完全阻断，而β2-肾上腺素受体特异性激动剂沙美特罗则明显增强 REDD1 的表达。此外，去甲肾上腺素在高于肾上腺素有效剂量的剂量下增加 REDD1 mRNA 的表达。膜可渗透的 cAMP 类似物 8-Br-cAMP 处理可模拟肾上腺素对 REDD1 mRNA 表达的作用。因此，β2-肾上腺素受体刺激引起的细胞内 cAMP 水平增加似乎负责肾上腺素诱导的 REDD1 mRNA 表达。然而，在β2-肾上腺素受体刺激后，抑制蛋白激酶 A（PKA）活性对 REDD1 mRNA 表达没有显著影响。此外，cAMP 激活的交换蛋白（Epac）激动剂 8-CPT-20-O-Me-cAMP 对 REDD1 mRNA 表达没有影响。因此，β2-肾上腺素受体介导的 cAMP 水平增加似乎通过 PKA 和 Epac 独立途径诱导巨噬细胞中 REDD1 mRNA 的表达。
