Activated protein C inhibits bronchial hyperresponsiveness and Th2 cytokine expression in mice.
Activated protein C inhibits bronchial hyperresponsiveness and Th2 cytokine expression in mice.
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DOI：
10.1182/blood-2003-06-1980
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发表时间：
2004-03
期刊：
影响因子：
20.3
通讯作者：
H. Yuda;Y. Adachi;O. Taguchi;E. Gabazza;O. Hataji;H. Fujimoto;S. Tamaki;K. Nishikubo;K. Fukudome-K.-Fuk
中科院分区：
文献类型：
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作者：
H. Yuda;Y. Adachi;O. Taguchi;E. Gabazza;O. Hataji;H. Fujimoto;S. Tamaki;K. Nishikubo;K. Fukudome-K.-Fuk
哮喘是最常见的疾病之一，其特征是气道阻塞、气道炎症和气道反应性增加。糖皮质激素治疗非常有效，但长期使用会产生多种副作用，因此新的抗炎药物正在开发中。活化蛋白 C (APC) 是一种丝氨酸蛋白酶，具有有效的抗炎作用。本研究评估了吸入 APC 对小鼠哮喘模型中气道炎症和高反应性的影响。 BALB/c 小鼠通过暴露于鸡蛋卵清蛋白 (OVA) 诱发哮喘，并通过在暴露于 OVA 之前施用来评估吸入 APC 的效果。吸入 APC 可显着抑制辅助性 T 2 (Th2) 细胞因子、免疫球蛋白 E (IgE) 的表达、嗜酸性粒细胞炎症和高反应性。 APC 还显着抑制从 OVA 致敏/攻击动物中分离的淋巴细胞中 Th2 细胞因子和 IgE 的表达。此外，在吸入 APC 治疗的小鼠中，信号转导器和转录激活剂 6 (STAT6) 和核因子 kappa B (NF-kappa B) 寡核苷酸与肺核蛋白的结合显着减少。简而言之，外源性补充 APC 可抑制哮喘小鼠模型中 Th2 细胞因子诱导的免疫和炎症反应，可能代表一种新型抗炎治疗方法。
Asthma is one of the most common diseases and is characterized by airway obstruction, airway inflammation, and increased airway responsiveness. Glucocorticoids are very effective in treatment, but their long-term use is associated with several side effects, so that new anti-inflammatory drugs are in development. Activated protein C (APC) is a serine protease with potent anti-inflammatory effects. This study evaluated the effect of inhaled APC on airway inflammation and hyperresponsiveness in a murine asthma model. Asthma was induced in BALB/c mice by exposure to chicken egg ovalbumin (OVA), and the effect of inhaled APC was assessed by administering prior to OVA exposure. Inhalation of APC significantly inhibited the expression of T helper 2 (Th2) cytokines, immunoglobulin E (IgE), eosinophilic inflammation, and hyperresponsiveness. APC also significantly suppressed the expression of Th2 cytokines and IgE from lymphocytes isolated from OVA-sensitized/challenged animals. In addition, binding of signal transducer and activator of transcription 6 (STAT6) and nuclear factor kappa B (NF-kappa B) oligonucleotides to lung nuclear proteins was significantly reduced in mice treated with inhaled APC. In brief, the exogenous supplementation of APC inhibits the immunologic and inflammatory responses induced by Th2 cytokines in a mouse model of asthma and may represent a novel anti-inflammatory treatment.