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

Umasundari Sivaprasad, David J. Askew, Mark B. Ericksen, Aaron M. Gibson, Matthew T. Stier, Eric B. Brandt, Stacey A. Bass, Michael O. Daines, Jamila Chakir, Keith F. Stringer, Susan E. Wert, Jeffrey A. Whitsett, Timothy D. Le Cras, Marsha Wills-Karp, Gary A. Silverman, Gurjit K. Khurana Hershey

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)254-261.e6
JournalJournal of Allergy and Clinical Immunology
Volume127
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • IL-13
  • SPDEF
  • goblet cells
  • hyperplasia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sivaprasad, U., Askew, D. J., Ericksen, M. B., Gibson, A. M., Stier, M. T., Brandt, E. B., Bass, S. A., Daines, M. O., Chakir, J., Stringer, K. F., Wert, S. E., Whitsett, J. A., Le Cras, T. D., Wills-Karp, M., Silverman, G. A., & Khurana Hershey, G. K. (2011). A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma. Journal of Allergy and Clinical Immunology, 127(1), 254-261.e6. https://doi.org/10.1016/j.jaci.2010.10.009