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

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

来源：Journal of Allergy and Clinical Immunology, 2011, 127(1): 254-U418.

DOI：10.1016/j.jaci.2010.10.009

• Goblet cells
• SPDEF
• IL-13
• hyperplasia

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.)

• 出版日期2011-1