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J Allergy Clin Immunol. 2011 Jan;127(1):254-61, 261.e1-6. doi: 10.1016/j.jaci.2010.10.009. Epub 2010 Dec 3.

A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma.

Author information

  • 1Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio 45229, USA.

Abstract

BACKGROUND:

Asthma is a major public health burden worldwide. Studies from our group and others have demonstrated that SERPINB3 and SERPINB4 are induced in patients with asthma; however, their mechanistic role in asthma has yet to be determined.

OBJECTIVE:

To evaluate the role of Serpin3a, the murine homolog of SERPINB3 and SERPINB4, in asthma.

METHODS:

We studied wild-type Balb/c and Serpinb3a-null mice in house dust mite or IL-13-induced asthma models and evaluated airway hyperresponsiveness, inflammation, and goblet cell hyperplasia.

RESULTS:

Airway hyperresponsiveness and goblet cell hyperplasia were markedly attenuated in the Serpinb3a-null mice compared with the wild-type mice after allergen challenge, with minimal effects on inflammation. Expression of sterile alpha motif pointed domain containing v-ets avian erythroblastosis virus E26 oncogene homolog transcription factor (SPDEF), a transcription factor that mediates goblet cell hyperplasia, was decreased in the absence of Serpinb3a. IL-13-treated Serpinb3a-null mice showed attenuated airway hyperresponsiveness, inflammation, and mucus production.

CONCLUSION:

Excessive mucus production and mucus plugging are key pathologic features of asthma, yet the mechanisms responsible for mucus production are not well understood. Our data reveal a novel nonredundant role for Serpinb3a in mediating mucus production through regulation of SPDEF expression. This pathway may be used to target mucus hypersecretion effectively.

Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

PMID:
21126757
[PubMed - indexed for MEDLINE]
PMCID:
PMC3058372
Free PMC Article

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