Department of Military Nautical Medicine, Laboratory of Stress Medicine, Faculty of Naval Medicine, Second Military Medical University, Xiangyin Road 800, Shanghai 200433, People's Republic of China.
Inflammation. 2012 Apr;35(2):527-34. doi: 10.1007/s10753-011-9342-4.
The aim of this study was to investigate whether norepinephrine (NE) could regulate macrophage production of tumor necrosis factor alpha (TNF-α) by influencing the phosphorylation of mitogen-activated protein kinases (MAPKs). Primary macrophages from male BALB/c mice were applied to explore the mechanism by which NE influences the the secretion of TNF-α when macrophages were activated by lipopolysaccharides (LPS). We found that NE could increase crophage production of TNF-α when macrophages were activated by LPS, and this effect could be inhibited by α adrenergic antagonist phentolamine. Also, NE could increase the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases (ERK), and p38, through α receptor. Furthermore, JNK inhibitor SP600125, ERK inhibitor U0126, and p38 inhibitor SB203580 could all partially counteract NE's effect on the phosphorylation of MAPKs, as well as TNF-α production by macrophages. This study revealed that as macrophages were activated by LPS, NE promoted the secretion of inflammatory factors by increasing the phosphorylation of MAPKs through an α receptor-dependent pathway. Our results provide the evidence of a relationship between stress and diseases, as well as the mechanism by which stress induces or affects the inflammation-related diseases.
本研究旨在探讨去甲肾上腺素（NE）是否通过影响丝裂原活化蛋白激酶（MAPKs）的磷酸化来调节巨噬细胞产生肿瘤坏死因子-α（TNF-α）。应用雄性 BALB/c 小鼠原代巨噬细胞，探索 NE 影响 LPS 激活巨噬细胞时 TNF-α分泌的机制。我们发现，NE 可以增加 LPS 激活的巨噬细胞 TNF-α的产生，而这种作用可以被α肾上腺素能拮抗剂酚妥拉明抑制。此外，NE 通过α受体增加 c-Jun N 末端激酶（JNK）、细胞外信号调节激酶（ERK）和 p38 的磷酸化。进一步的，JNK 抑制剂 SP600125、ERK 抑制剂 U0126 和 p38 抑制剂 SB203580 均可部分拮抗 NE 对 MAPKs 磷酸化以及巨噬细胞 TNF-α产生的作用。本研究揭示，在 LPS 激活的巨噬细胞中，NE 通过α受体依赖性途径增加 MAPKs 的磷酸化，促进炎症因子的分泌。我们的结果为应激与疾病之间的关系以及应激诱导或影响炎症相关疾病的机制提供了证据。
