Liu Yi, Wang Gu-Yi, Liu Shao-Kun, Yang Mu-Yi, Ma Li-Bing, Li Keng, Gong Su-Bo, Zhang Li, Chen Ping, Xiang Xu-Dong
Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
Iran J Allergy Asthma Immunol. 2011 Sep;10(3):171-82.
Allergic asthma is a complex and chronic inflammatory airway disease. Interleukin-17 is a pro-inflammatory cytokine which plays critical role in the pathogenesis of allergic asthma. It has been reported that β-arrestin2 regulated the development of allergic asthma at a proximal step in the inflammatory cascade. In this study, the influence of β-arrestin2 on Interleukin-17 production and expression of CD4+ T lymphocytes in a murine asthma model was investigated. Splenic CD4+ T lymphocytes from wild-type mice and those from a murine asthma model were purified. CD4+ T lymphocytes from a murine asthma model were transfected with siRNAs targeting the β-arrestin2 or were pretreated with the ERK1/2 inhibitor, PD98059. After stimulation, the protein expression of β-arrestin2、phosphorylated-ERK1/2 and IL-17 were detection by Western blot; the mRNA expression of IL-17 were detected by real-time PCR; the accumulation of IL-17 in supernatants were detected by ELISA. We found that β-arrestin2、phosphorylated-ERK1/2 and IL-17 expression in CD4+ T lymphocytes from a murine asthma model were increased compared with those from wild-type mice (p < 0.01). Treatment of CD4+ T lymphocytes with siRNAs targeting the β-arrestin2 down-regulated phosphorylated- ERK 1/2 and IL-17 expression (p < 0.01). PD98059 decreased IL-17 production and expression in CD4+ T lymphocytes in a murine asthma model (p < 0.05). We conclude that β-arrestin2 stimulated IL-17 production and expression of CD4+ T lymphocytes in a murine asthma model. The effect was partly mediated by ERK 1/2 activation. Targeting β-arrestin2 biological activity could be a valid therapeutic approach for the treatment of allergic asthma.
过敏性哮喘是一种复杂的慢性炎症性气道疾病。白细胞介素-17是一种促炎细胞因子，在过敏性哮喘的发病机制中起关键作用。据报道，β-抑制蛋白2在炎症级联反应的近端步骤调节过敏性哮喘的发展。在本研究中，研究了β-抑制蛋白2对小鼠哮喘模型中白细胞介素-17产生及CD4+T淋巴细胞表达的影响。纯化野生型小鼠和小鼠哮喘模型的脾CD4+T淋巴细胞。用靶向β-抑制蛋白2的小干扰RNA转染小鼠哮喘模型的CD4+T淋巴细胞，或用ERK1/2抑制剂PD98059进行预处理。刺激后，通过蛋白质印迹法检测β-抑制蛋白2、磷酸化ERK1/2和IL-17的蛋白表达；通过实时PCR检测IL-17的mRNA表达；通过酶联免疫吸附测定法检测上清液中IL-17的积累。我们发现，与野生型小鼠相比，小鼠哮喘模型的CD4+T淋巴细胞中β-抑制蛋白2、磷酸化ERK1/2和IL-17的表达增加（p<0.01）。用靶向β-抑制蛋白2的小干扰RNA处理CD4+T淋巴细胞可下调磷酸化ERK1/2和IL-17的表达（p<0.01）。PD98059可降低小鼠哮喘模型CD4+T淋巴细胞中IL-17的产生和表达（p<0.05）。我们得出结论，在小鼠哮喘模型中，β-抑制蛋白2刺激CD4+T淋巴细胞产生IL-17并使其表达。该作用部分由ERK1/2激活介导。靶向β-抑制蛋白2的生物学活性可能是治疗过敏性哮喘的有效治疗方法。
