Title:Comparison of Airway Remodeling in Acute, Subacute, and Chronic Models of Allergic Airways Disease
Author:Natasha R. Locke
Abstract:
The relationship between airway inflammation and structural changes of airway remodeling, and their relative effects on airway function, are poorly understood. Remodeling is thought to result from chronic repetitive injury to the airway wall caused by airway inflammation; however, the mechanisms regulating remodeling changes have not been clearly defined. We examined the sequence of events in remodeling using three commonly used mouse models of allergic airways disease in which mice are exposed to nebulized ovalbumin for four consecutive days (acute), seven consecutive days (subacute), or three times a week for 6 wk (chronic). Surprisingly, we found that a very short period of exposure to ovalbumin was sufficient to elicit early changes of remodeling. Goblet cell hyperplasia and epithelial thickening were evident after just 4 d. In chronically challenged mice, these changes persisted and, in addition, subepithelial collagen deposition was significantly increased. This collagen deposition was associated with a failure to upregulate matrix metalloproteinase (MMP)-2, in conjunction with increased transforming growth factor- and MMP-9 expression. The relationship between inflammation, remodeling changes, and airway hyperresponsiveness (AHR) were examined. The acute and subacute models exhibited marked airway inflammation, whereas the chronic model had very modest inflammation. Conversely, airway fibrosis was only evident in the chronic model. AHR was present in all three models; however, it was significantly higher in the chronic model compared with the acute (P < 0.05) and subacute (P < 0.05) models. These data demonstrate that both airway inflammation and airway fibrosis may contribute to AHR, with airway fibrosis leading to the greatest increases in AHR.
Key Words: asthma • fibrosis • inflammation • mice
American Journal of Respiratory Cell and Molecular Biology. Vol. 36, pp. 625-632, 2007
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Title:Comparison of Airway Remodeling in Acute, Subacute, and Chronic Models of
Allergic Airways Disease
标题：急性、亚急性、慢性过敏性气道疾病模型中气道重构的比较
Author:Natasha R. Locke
作者：Natasha R. Locke
Abstract:
The relationship between airway inflammation and structural changes of airway
remodeling, and their relative effects on airway function, are poorly understood. Remodeling is thought to result from chronic repetitive injury to
the airway wall caused by airway inflammation; however, the mechanisms
regulating remodeling changes have not been clearly defined. We examined the
sequence of events in remodeling using three commonly used mouse models of allergic airways disease in which mice are exposed to nebulized ovalbumin for four consecutive days (acute), seven consecutive days (subacute), or three times a week for 6 wk (chronic). Surprisingly, we found that a very short period of exposure to ovalbumin was sufficient to elicit early changes of remodeling. Goblet cell hyperplasia and epithelial thickening were evident after just 4 d. In chronically challenged mice, these changes persisted and, in addition, subepithelial collagen deposition was significantly increased.
This collagen deposition was associated with a failure to upregulate matrix
metalloproteinase (MMP)-2, in conjunction with increased transforming growth
factor- and MMP-9 expression. The relationship between inflammation, remodeling changes, and airway hyperresponsiveness (AHR) were examined. The acute and subacute models exhibited marked airway inflammation, whereas the chronic model had very modest inflammation. Conversely, airway fibrosis was only evident in the chronic model. AHR was present in all three models; however, it was significantly higher in the chronic model compared with the acute (P < 0.05) and subacute (P < 0.05) models. These data demonstrate that both airway inflammation and airway fibrosis may contribute to AHR, with airway fibrosis leading to the greatest increases in AHR.
气道炎症与气道重构结构改变之间的联系和它们对气道功能的影响知之甚少。重构被认为是气道炎症导致的气道壁慢性反复性损伤；然而重构改变的调节机制还不十分清楚。我们利用三种常用的变应性气道疾病的大鼠模型来观察重构的序列事件，老鼠暴露于雾化卵白蛋白连续四天（急性），暴露七天（亚急性），或者一周三次共六周（慢性）。令人惊讶的是，我们发现暴露于卵白蛋白极短时间足够显示重构的早期改变。暴露四天后，杯状细胞增生和上皮变厚就很明显。在慢性改变的老鼠中，这些改变持续并且还有上皮下胶原沉着显著增加。胶原沉着与MMP-2下调有关，联合TGF和MMP-9表达增加。我们研究了炎症，重构改变和气道高反应性之间的联系。急性和亚急性组表现明显的气道炎症，而慢性组显示中度炎症。相反，气道纤维化仅仅在慢性组明显。气道高反应性在三组中都存在，然而慢性模型组显著高于亚急性(P < 0.05)和急性组(P < 0.05)。结果显示气道炎症和气道纤维化都导致气道高反应性，气道纤维化引起的气道反应性增高最大。
Key Words: asthma ? fibrosis ? inflammation ? mice
关键词：哮喘、纤维化、炎症、大鼠
American Journal of Respiratory Cell and Molecular Biology. Vol. 36, pp. 625-
632, 2007
