IL-4 coordinates the Th2-type immune response in inflammatory diseases such as asthma. IL-27 can inhibit the development of both Th2 and Th1 cells. However, IL-27 can also drive naïve T cells to differentiate toward the Th1 phenotype. In this study, we investigated the effects of IL-27 on the activation of IL-4-induced human bronchial epithelial cells (BEAS-2B). Compared to controls, both IL-4 and IL-27 (25–100 ng/mL) increased the concentrations of CCL2 and IL-8 in a dose-dependent manner. However, compared to cells stimulated individually with IL-4 or IL-27, treatment with a combination of both cytokines reduced CCL2 and IL-8 concentrations in a dose- and time-dependent manner. IL-4 increased the activation of p38 MAPK, ERK1/2, STAT6 and NF-κB, while IL-27 increased the activation of p38 MAPK and ERK1/2 but not STAT6 and NF-κB. Compared to IL-4-stimulated cells, cells treated with both IL-27 and IL-4 displayed decreased activation of STAT6 and NF-κB but not ERK1/2 and p38 MAPK. Taken together, these results suggest that IL-27 plays a pro-inflammatory role when administered alone but downregulates bronchial epithelial cell activation when combined with IL-4. Therefore, IL-27 may be an interesting target for the treatment of Th2 inflammatory diseases.

IL-4 在哮喘等炎症性疾病中协调 Th2 型免疫反应。IL-27 可以抑制 Th2 和 Th1 细胞的发育。然而，IL-27 也可以驱动幼稚 T 细胞向 Th1 表型分化。在这项研究中，我们研究了 IL-27 对 IL-4 诱导的人支气管上皮细胞 (BEAS-2B) 活化的影响。与对照组相比，IL-4 和 IL-27 (25–100 ng/mL) 均以剂量依赖性方式增加 CCL2 和 IL-8 的浓度。然而，与用 IL-4 或 IL-27 单独刺激的细胞相比，用两种细胞因子的组合治疗以剂量和时间依赖性方式降低了 CCL2 和 IL-8 浓度。IL-4 增加 p38 MAPK、ERK1/2、STAT6 和 NF-κB 的活化，而 IL-27 增加 p38 MAPK 和 ERK1/2 的活化，但不增加 STAT6 和 NF-κB 的活化。与 IL-4 刺激的细胞相比，用 IL-27 和 IL-4 处理的细胞显示出 STAT6 和 NF-κB 的激活减少，但 ERK1/2 和 p38 MAPK 没有。总之，这些结果表明，IL-27 在单独给药时发挥促炎作用，但在与 IL-4 联合使用时会下调支气管上皮细胞的活化。因此，IL-27 可能是治疗 Th2 炎性疾病的一个有趣的靶点。