Lee K S, Jin S M, Lee H, Lee Y C
Department of Internal Medicine, Research Center for Allergic Immune Diseases, Chonbuk National University Medical School, Jeonju, South Korea.
Clin Exp Allergy. 2004 Feb;34(2):276-84. doi: 10.1111/j.1365-2222.2004.01849.x.
Toluene diisocyanate (TDI)-induced asthma is an inflammatory disease of the airways characterized by airway remodelling due, at least in part, to an excess of extracellular matrix deposition in the airway wall. The ratio of matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) may be a marker of the balance between airway tissue destruction and repair.
We determined whether an imbalance of the MMP-9 : TIMP-1 molar ratio is present before and/or after challenge with TDI.
We used a murine model of TDI-induced asthma to evaluate the MMP-9 and TIMP-1 balance in the lung.
The expression of MMP-9 and TIMP-1 mRNAs and proteins in the lungs increased at 7 h after TDI inhalation and continued for up to 72 h. Immunohistochemical and immunocytological analyses in the lungs of TDI-exposed mice revealed increases of immunoreactive MMP-9 and TIMP-1. There were significant correlations between the levels of MMP-9 or TIMP-1 and the number of neutrophils, lymphocytes, or eosinophils. The molar ratio of MMP-9/TIMP-1 significantly decreased at 7 h after TDI inhalation and continued up to 72 h.
These data suggest that TDI-induced asthma may be associated with an imbalance between MMP-9 and TIMP-1, which could be useful as a marker of airway inflammation and airway remodelling in this disease.
甲苯二异氰酸酯（TDI）诱发的哮喘是一种气道炎症性疾病，其特征在于气道重塑，这至少部分归因于气道壁中细胞外基质沉积过多。基质金属蛋白酶-9（MMP-9）与其抑制剂金属蛋白酶组织抑制剂-1（TIMP-1）的比例可能是气道组织破坏与修复之间平衡的一个标志物。
我们确定在TDI激发之前和/或之后是否存在MMP-9：TIMP-1摩尔比失衡。
我们使用TDI诱发哮喘的小鼠模型来评估肺中MMP-9和TIMP-1的平衡。
吸入TDI后7小时，肺中MMP-9和TIMP-1的mRNA及蛋白表达增加，并持续至72小时。对暴露于TDI的小鼠肺组织进行免疫组织化学和免疫细胞分析显示，免疫反应性MMP-9和TIMP-1增加。MMP-9或TIMP-1水平与中性粒细胞、淋巴细胞或嗜酸性粒细胞数量之间存在显著相关性。吸入TDI后7小时，MMP-9/TIMP-1摩尔比显著降低，并持续至72小时。
这些数据表明，TDI诱发的哮喘可能与MMP-9和TIMP-1之间的失衡有关，这可能作为该疾病气道炎症和气道重塑的一个标志物。
