Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 127, Issue 1, Pages 254-U418Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2010.10.009
Keywords
Goblet cells; SPDEF; IL-13; hyperplasia
Categories
Funding
- NIH [U19AI70235-01, AI58157-01]
- American Heart Association [740069N, PO1 HL076383, U19AI070235, NIH DK081422]
- Cystic Fibrosis Foundation
- NIH
- American Heart Association
- [HL090156]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL076383, R01HL095580, R01HL090156] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI083403, U19AI070235, R01AI058157] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK081422] Funding Source: NIH RePORTER
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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. IL13-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. (J Allergy Clin Immunol 2011;127:254-61.)
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