目的 探讨干扰素λ1（interferon-λ1, IFN-λ1）对呼吸道合胞病毒（respiratory syncytial virus, RSV）刺激下的人支气管上皮细胞（human bronchial epithelial cell, HBEC）糖皮质激素（glucocorticoid, GC）抵抗的影响。 方法 将HBEC分为对照组、地塞米松（dexamethasone, Dex）组、IFN-λ1组、RSV组、RSV+IFN-λ1组。采用CCK-8法测定不同浓度IFN-λ1对HBEC细胞活力的影响及各组HBEC对地塞米松的敏感性，实时荧光定量PCR法测定p38丝裂原活化蛋白激酶（p38 mitogen-activated protein kinase, p38 MAPK）、糖皮质激素受体（glucocorticoid receptor, GR）、MAPK磷酸酶-1（MAPK phosphatase-1, MKP-1）mRNA表达，Western blot法测定细胞核、细胞质GR蛋白表达，并计算细胞核GR蛋白量/细胞质GR蛋白量比值。 结果 24 h、72 h时，随IFN-λ1浓度增加，HBEC细胞增殖活性增加，且呈浓度和时间依赖性（P˂0.05）；与RSV组比较，RSV+IFN-λ1组地塞米松的半数最大抑制浓度、p38 MAPK mRNA表达水平降低（P˂0.05），GR、MKP-1 mRNA表达水平、细胞核与细胞质GR水平及细胞核GR/细胞质GR比值升高（P<0.05）。 结论 IFN-λ1可通过上调MKP-1抑制p38 MAPK通路，促进GR的核转移，从而改善HBEC细胞GC抵抗。
Objective To investigate the effect of interferon-λ1 (IFN-λ1) on glucocorticoid (GC) resistance in human bronchial epithelial cells (HBECs) stimulated by respiratory syncytial virus (RSV). Methods HBECs were divided into five groups: control, dexamethasone, IFN-λ1, RSV, and RSV+IFN-λ1. CCK-8 assay was used to measure the effect of different concentrations of IFN-λ1 on the viability of HBECs, and the sensitivity of HBECs to dexamethasone was measured in each group. Quantitative real-time PCR was used to measure the mRNA expression levels of p38 mitogen-activated protein kinase (p38 MAPK), glucocorticoid receptor (GR), and MAPK phosphatase-1 (MKP-1). Western blot was used to measure the protein expression level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic ratio of GR was calculated. Results At 24 and 72 hours, the proliferation activity of HBECs increased with the increase in IFN-λ1 concentration in a dose- and time-dependent manner (P˂0.05). Compared with the RSV group, the RSV+IFN-λ1 group had significant reductions in the half-maximal inhibitory concentration of dexamethasone and the mRNA expression level of p38 MAPK (P<0.05), as well as significant increases in the mRNA expression levels of GR and MKP-1, the level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic GR ratio (P<0.05). Conclusions IFN-λ1 can inhibit the p38 MAPK pathway by upregulating MKP-1, promote the nuclear translocation of GR, and thus ameliorate GC resistance in HBECs.
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