Additive anti-inflammatory effects of corticosteroids and phosphodiesterase-4 inhibitors in COPD CD8 cells.
Additive anti-inflammatory effects of corticosteroids and phosphodiesterase-4 inhibitors in COPD CD8 cells.
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DOI：
10.1186/s12931-016-0325-8
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发表时间：
2016-01-25
影响因子：
5.8
通讯作者：
Singh D
中科院分区：
文献类型：
--
作者：
Grundy S;Plumb J;Kaur M;Ray D;Singh D
CD 8淋巴细胞在COPD的发病中起重要作用。皮质类固醇和磷酸二酯酶4（PDE 4）抑制剂是用于COPD治疗的抗炎药。我们研究了糖皮质激素与PDE 4抑制剂联合应用对循环和肺CD 8细胞释放细胞因子及糖皮质激素（GR）核转位的影响。测量地塞米松单独和与PDE 4抑制剂罗氟司特和GSK 256066组合对从循环和肺CD 8细胞释放细胞因子的作用。使用免疫荧光研究了化合物对GR和环AMP反应元件结合蛋白（CREB）核转位的影响。地塞米松以浓度依赖性方式抑制COPD CD 8细胞的细胞因子释放。PDE 4抑制剂以相加的方式增强了这种抗炎作用。PDE 4抑制剂不增加皮质类固醇诱导的GR核转位。PDE 4抑制剂，而不是皮质类固醇，增加磷酸化CREB核转位。皮质类固醇和PDE 4抑制剂的组合导致COPD CD 8细胞中的附加抗炎作用。这种增强的抗炎作用可以转化为COPD患者的重要临床益处。本文的在线版本（doi：10.1186/s12931-016-0325-8）包含补充材料，可供授权用户使用。
CD8 lymphocytes play an important role in the pathogenesis of COPD. Corticosteroids and phosphodiesterase 4 (PDE4) inhibitors are anti-inflammatory drugs used for COPD treatment. Little is known of the combined effect of these drugs on COPD CD8 cells. We studied the effect of corticosteroid combined with PDE4 inhibitors on cytokine release form circulating and pulmonary CD8 cells, and on glucocorticoid (GR) nuclear translocation. The effect of dexamethasone alone and in combination with the PDE4 inhibitors roflumilast and GSK256066 on cytokine release from circulating and pulmonary CD8 cells was measured. The effect of the compounds on nuclear translocation of GR and cyclic AMP-responsive element-binding protein (CREB) was studied using immunofluorescence. Dexamethasone inhibited cytokine release from COPD CD8 cells in a concentration dependent manner. PDE4 inhibitors enhanced this anti-inflammatory effect in an additive manner. PDE4 inhibitors did not increase corticosteroid induced GR nuclear translocation. PDE4 inhibitors, but not corticosteroid, increased phospho-CREB nuclear translocation. The combination of corticosteroids and PDE4 inhibitors results in an additive anti-inflammatory effect in COPD CD8 cells. This enhanced anti-inflammatory effect could translate to important clinical benefits for patients with COPD. The online version of this article (doi:10.1186/s12931-016-0325-8) contains supplementary material, which is available to authorized users.