Keränen Tiina, Hömmö Tuija, Moilanen Eeva, Korhonen Riku
The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, Tampere, Finland.
The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, Tampere, Finland.
Cytokine. 2017 Jun;94:1-7. doi: 10.1016/j.cyto.2016.07.016. Epub 2017 Feb 3.
β-receptor agonists are used in the treatment of inflammatory obstructive lung diseases asthma and COPD as a symptomatic remedy, but they have been suggested to possess anti-inflammatory properties, also. β-receptor activation is considered to lead to the activation of ERK pathway through G-protein- and cAMP-independent mechanisms. In this study, we investigated the effects of β-receptor agonists salbutamol and terbutaline on the production of inflammatory factors in macrophages. We found that β-receptor agonists inhibited LPS-induced ERK phosphorylation and the production of MCP-1. A chemical cAMP analog 8-Br-cAMP also inhibited ERK phosphorylation and TNF and MCP-1 release. As expected, MAPK/ERK kinase (MEK)1/2 inhibitor PD0325901 inhibited ERK phosphorylation and suppressed both TNF and MCP-1 production. In conclusion, we suggest that β-receptor agonists salbutamol and terbutaline inhibit inflammatory gene expression partly by a mechanism dependent on cAMP leading to the inhibition of ERK signaling in macrophages. Observed anti-inflammatory effects of β-receptor agonists may contribute to the clinical effects of these drugs.
β受体激动剂作为一种对症治疗药物，用于治疗炎症性阻塞性肺疾病如哮喘和慢性阻塞性肺疾病（COPD），但也有人认为它们具有抗炎特性。β受体激活被认为可通过不依赖G蛋白和环磷酸腺苷（cAMP）的机制导致细胞外信号调节激酶（ERK）通路的激活。在本研究中，我们调查了β受体激动剂沙丁胺醇和特布他林对巨噬细胞中炎症因子产生的影响。我们发现β受体激动剂抑制脂多糖（LPS）诱导的ERK磷酸化以及单核细胞趋化蛋白-1（MCP-1）的产生。一种化学合成的cAMP类似物8-溴-cAMP也抑制ERK磷酸化以及肿瘤坏死因子（TNF）和MCP-1的释放。正如预期的那样，丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）激酶（MEK）1/2抑制剂PD0325901抑制ERK磷酸化，并抑制TNF和MCP-1的产生。总之，我们认为β受体激动剂沙丁胺醇和特布他林部分通过一种依赖cAMP的机制抑制炎症基因表达，从而导致巨噬细胞中ERK信号传导的抑制。观察到的β受体激动剂的抗炎作用可能有助于这些药物的临床疗效。
