A Potential New Target for Asthma Therapy: A Disintegrin and Metalloprotease 10 (ADAM10) Involvement in Murine Experimental Asthma

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Christopher Kepley, Associate Professor (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: Background: Elevated levels of CD23, a natural regulator of IgE production, have been shown to decrease the signs of lung inflammation in mice. The aim of this study was to study the involvement of ADAM10, the primary CD23 sheddase, in experimental asthma. Methods: ADAM10 was blocked either by using mice with a B-cell-specific deletion of the protease or pharmacologically by intranasal administration of selective ADAM10 inhibitors. Airway hypersensitivity (AHR) and bronchoaveolar lavage fluid (BALF) eosinophilia and select BALF cytokine/chemokine levels were then determined. Results: Using an IgE and mast cell–dependent mouse model, B-cell-specific ADAM10-/- mice (C57B/6 background) exhibited decreased eosinophilia and AHR when compared with littermate (LM) controls. Treatment of C57B/6 mice with selective inhibitors of ADAM10 resulted in an even further decrease in BALF eosinophilia, as compared with the ADAM10-/- animals. Even in the Th2 selective strain, Balb/c, BALF eosinophilia was reduced from 60% to 23% respectively. In contrast, when an IgE/mast cell–independent model of lung inflammation was used, the B-cell ADAM10-/- animals and ADAM10 inhibitor treated animals had lung inflammation levels that were similar to the controls. Conclusions: These results thus show that ADAM10 is important in the progression of IgE-dependent lung inflammation. The use of the inhibitor further suggested that ADAM10 was important for maintaining Th2 levels in the lung. These results thus suggest that decreasing ADAM10 activity could be beneficial in controlling asthma and possibly other IgE-dependent diseases.

Additional Information

Allergy, 66(9): 1193–1200
Language: English
Date: 2011
ADAM10, asthma, CD23, IgE, Th2

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