The Immunopharmacology Research Group, University of Tampere School of Medicine, and Tampere University Hospital, University of Tampere, FI-33014, Tampere, Finland.
Inflamm Res. 2017 May;66(5):441-449. doi: 10.1007/s00011-017-1028-4. Epub 2017 Mar 15.
Mitogen-activated protein kinase phosphatase 1 (MKP-1) expression is induced by inflammatory factors and serves as an endogenous p38 MAPK suppressor to limit inflammatory response. Glucocorticoids are very effective anti-inflammatory drugs and they are used for the treatment of many inflammatory diseases, such as asthma and COPD. We investigated the role of MKP-1 in the inhibition of cytokine production by dexamethasone in human A549 bronchial epithelial cells. We found that dexamethasone increased MKP-1 expression, inhibited p38 MAPK phosphorylation, and suppressed TNF and MIP-3α production in A549 cells. Interestingly, the suppression of p38 MAPK phosphorylation and the inhibition of TNF expression by dexamethasone were attenuated in cells, where MKP-1 expression was silenced by siRNA. In conclusion, these data suggest that dexamethasone increases MKP-1 expression and this results in the suppression of p38 MAPK signaling leading to the inhibition of cytokine production in human bronchial epithelial cells. These results point to the role of MKP-1 as an important factor in the therapeutic effects of glucocorticoids in the treatment of inflammatory lung diseases.
丝裂原活化蛋白激酶磷酸酶 1（MKP-1）的表达受炎症因子诱导，作为内源性 p38MAPK 抑制剂，限制炎症反应。糖皮质激素是非常有效的抗炎药物，用于治疗许多炎症性疾病，如哮喘和 COPD。我们研究了 MKP-1 在人 A549 支气管上皮细胞中抑制细胞因子产生中的作用。我们发现地塞米松增加了 MKP-1 的表达，抑制了 p38MAPK 的磷酸化，并抑制了 A549 细胞中 TNF 和 MIP-3α 的产生。有趣的是，沉默 MKP-1 表达的 siRNA 减弱了地塞米松对 p38MAPK 磷酸化的抑制和 TNF 表达的抑制作用。总之，这些数据表明，地塞米松增加了 MKP-1 的表达，从而抑制了 p38MAPK 信号通路，导致人支气管上皮细胞中细胞因子的产生受到抑制。这些结果表明 MKP-1 是糖皮质激素治疗炎症性肺部疾病疗效的重要因素。
