Chiba Yoshihiko, Srisodsai Achara, Supavilai Porntip, Kimura Shioko
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Immunol Lett. 2005 Feb 15;97(1):123-9. doi: 10.1016/j.imlet.2004.10.013.
Airway inflammation is thought to play a major role in the pathogenesis of bronchial asthma. The precise role of individual inflammatory cells, mediator and asthma related genes in allergic lung diseases is not completely understood. The uteroglobin-related protein (UGRP) 1 was proposed to be an asthma candidate gene and play a role in regulating lung inflammation, however its precise function in the airways remains obscure. In this investigation, we used a mouse model of allergic airway inflammation to establish a relationship between UGRP 1 and IL-5 in airway inflammation. Ovalbumin (OVA) challenged mice demonstrate eosinophilia in airway tissues and high levels of IL-5 in bronchoalveolar lavage (BAL) fluid analogous to that found in bronchial asthma. Interestingly, these "OVA-challenged" mice show down-regulation of Ugrp1 expression as compared with the control group. Regression analysis further demonstrates a significant negative correlation between Ugrp1 mRNA expression in the lung and IL-5 levels in BAL fluid with r = 0.948 and P < 0.0001 when IL-5 levels were normalized by log transformation. Intranasal instillation of IL-5 to mice revealed an inhibitory effect of IL-5 on the expression of Ugrp1 mRNA. Together, these results indicate an involvement of IL-5 in the down-regulation of Ugrp1 expression in airway inflammation such as allergic asthma disease.
气道炎症被认为在支气管哮喘的发病机制中起主要作用。单个炎症细胞、介质和哮喘相关基因在过敏性肺疾病中的精确作用尚未完全明了。子宫珠蛋白相关蛋白(UGRP)1被认为是一个哮喘候选基因,在调节肺部炎症中发挥作用,然而其在气道中的精确功能仍不清楚。在本研究中,我们使用过敏性气道炎症小鼠模型来建立UGRP 1与白细胞介素-5(IL-5)在气道炎症中的关系。卵清蛋白(OVA)激发的小鼠气道组织出现嗜酸性粒细胞增多,支气管肺泡灌洗(BAL)液中IL-5水平升高,这与支气管哮喘中的情况类似。有趣的是,与对照组相比,这些“OVA激发”的小鼠Ugrp1表达下调。回归分析进一步表明,当通过对数转换对IL-5水平进行标准化时,肺中Ugrp1 mRNA表达与BAL液中IL-5水平之间存在显著负相关,r = 0.948,P < 0.0001。对小鼠进行鼻内滴注IL-5显示IL-5对Ugrp1 mRNA表达有抑制作用。总之,这些结果表明IL-5参与了过敏性哮喘等气道炎症中Ugrp1表达的下调。