Department of Pulmonary Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.
Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopedics and Traumatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7504-7512. doi: 10.3892/mmr.2017.7499. Epub 2017 Sep 18.
T cell‑associated inflammation, particularly type 2 inflammation, has an important role in asthma pathogenesis, which is suppressed by regulatory T cells (Tregs). Proviral integration site for Moloney murine leukemia virus 2 (PIM2), a member off the serine/threonine kinase family, promotes the growth and survival of T cells and influences the function of Treg cells. However, whether PIM2 affects asthma pathogenesis remains unclear. Peripheral blood mononuclear cells and Treg cells from asthmatic and healthy subjects were obtained, and the expression level of PIM2 was measured by reverse transcription‑quantitative polymerase chain reaction and immunocytochemistry. In addition, BALB/c female mice sensitized and challenged by ovalbumin were used as an asthma model, and PIM2 inhibitor was injected during the challenge period to observe the effect of PIM2 on asthma. The asthma symptoms were recorded, and airway hyper‑responsiveness (AHR), expression levels of cytokines in the serum or bronchoalveolar lavage fluid (BALF), and the number of BALF leukocytes were evaluated. In addition, hematoxylin and eosin staining and immunohistochemistry of lung tissues was performed. The results demonstrated that PIM2 was overexpressed in patients with asthma in natural Treg cells. Inhibition of PIM2 attenuated asthma symptoms, and improved AHR and airway inflammation compared with asthmatic mice without inhibition of PIM2. In addition, expression levels of interleukin (IL)‑10 and forkhead box protein 3 (FOXP3) in BALF were increased following PIM2 inhibition (IL‑10, 470.3±21.78 vs. 533.7±25.55 pg/ml, P<0.05; FOXP3, 259±4.68 vs. 279.3±3.68 pg/ml; asthma and PIM2 inhibition groups, respectively; P<0.05). In conclusion, PIM2 may exhibit an important role in asthma pathogenesis and exacerbate AHR, airway inflammation and asthma symptoms. These effects of PIM2 may be dependent on Treg cells and the secretion of IL‑10 by Tregs. The results of the present study suggest that PIM2 may be a potential target molecule for asthma treatment.
T 细胞相关炎症，特别是 2 型炎症，在哮喘发病机制中起重要作用，而调节性 T 细胞（Treg）可抑制该炎症。前病毒整合位点莫洛尼鼠白血病病毒 2（PIM2）是丝氨酸/苏氨酸激酶家族的成员，可促进 T 细胞的生长和存活，并影响 Treg 细胞的功能。然而，PIM2 是否影响哮喘发病机制尚不清楚。本研究从哮喘患者和健康受试者中获得外周血单核细胞和 Treg 细胞，通过逆转录-定量聚合酶链反应和免疫细胞化学测定 PIM2 的表达水平。此外，使用卵清蛋白致敏和攻击的 BALB/c 雌性小鼠作为哮喘模型，在攻击期间注射 PIM2 抑制剂，观察 PIM2 对哮喘的影响。记录哮喘症状，评估血清或支气管肺泡灌洗液（BALF）中细胞因子的表达水平以及 BALF 白细胞数量。此外，还进行了肺组织苏木精和伊红染色和免疫组织化学染色。结果表明，哮喘患者天然 Treg 细胞中 PIM2 表达过度。与未抑制 PIM2 的哮喘小鼠相比，抑制 PIM2 可减轻哮喘症状，并改善 AHR 和气道炎症。此外，抑制 PIM2 后 BALF 中白细胞介素（IL）-10 和叉头框蛋白 3（FOXP3）的表达水平增加（IL-10，470.3±21.78 与 533.7±25.55 pg/ml，P<0.05；FOXP3，259±4.68 与 279.3±3.68 pg/ml；哮喘和 PIM2 抑制组，分别；P<0.05）。综上所述，PIM2 可能在哮喘发病机制中起重要作用，并加重 AHR、气道炎症和哮喘症状。PIM2 的这些作用可能依赖于 Treg 细胞和 Treg 细胞分泌的 IL-10。本研究结果表明，PIM2 可能是哮喘治疗的潜在靶点分子。
