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

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.

Pubmed ID: 21126757

Authors

  • Sivaprasad U
  • Askew DJ
  • Ericksen MB
  • Gibson AM
  • Stier MT
  • Brandt EB
  • Bass SA
  • Daines MO
  • Chakir J
  • Stringer KF
  • Wert SE
  • Whitsett JA
  • Le Cras TD
  • Wills-Karp M
  • Silverman GA
  • Khurana Hershey GK

Journal

The Journal of allergy and clinical immunology

Publication Data

January 7, 2011

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI58157-01
  • Agency: NIDDK NIH HHS, Id: DK081422
  • Agency: NHLBI NIH HHS, Id: HL090156
  • Agency: NHLBI NIH HHS, Id: P01 HL076383
  • Agency: NIDDK NIH HHS, Id: R01 DK081422
  • Agency: NHLBI NIH HHS, Id: R01 HL095580
  • Agency: NIAID NIH HHS, Id: U19 AI070235
  • Agency: NIAID NIH HHS, Id: U19 AI070235-01
  • Agency: NIAID NIH HHS, Id: U19 AI070235-02
  • Agency: NIAID NIH HHS, Id: U19 AI070235-03
  • Agency: NIAID NIH HHS, Id: U19 AI070235-03S1
  • Agency: NIAID NIH HHS, Id: U19 AI070235-04
  • Agency: NIAID NIH HHS, Id: U19 AI070235-05
  • Agency: NIAID NIH HHS, Id: U19AI070235
  • Agency: NIAID NIH HHS, Id: U19AI70235-01

Mesh Terms

  • Animals
  • Asthma
  • Bronchoalveolar Lavage Fluid
  • Cell Separation
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression
  • Gene Expression Regulation
  • Goblet Cells
  • Immunoglobulin E
  • Immunoglobulin G
  • Immunohistochemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mucus
  • Proto-Oncogene Proteins c-ets
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serpins