Comparison of airway remodeling in acute, subacute, and chronic models of allergic airways disease

Natasha Locke, Simon Royce, Jacquetta Wainewright, Chrishan Samuel, Mimi Tang

Research output: Contribution to journalArticleResearchpeer-review

109 Citations (Scopus)

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-beta 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
Original languageEnglish
Pages (from-to)625 - 632
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume36
Issue number5
DOIs
Publication statusPublished - 2007
Externally publishedYes

Cite this

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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-beta 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",
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Comparison of airway remodeling in acute, subacute, and chronic models of allergic airways disease. / Locke, Natasha; Royce, Simon; Wainewright, Jacquetta; Samuel, Chrishan; Tang, Mimi.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 36, No. 5, 2007, p. 625 - 632.

Research output: Contribution to journalArticleResearchpeer-review

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