Surfactant protein-A protects against IL-13–induced inflammation in asthma

Dave Francisco, Ying Wang, Michelle Conway, Audriana N. Hurbon, Alane B.C. Dy, Kenneth J. Addison, Hong W. Chu, Dennis R. Voelker, Julie G. Ledford, Monica Kraft

Research output: Contribution to journalArticle

Abstract

The lung surfactant proteins are recognized as critical not only for their role in lowering lung surface tension but also in innate host defense. Reports have shown that some asthmatic patients have decreased levels of one member of this protein family in particular, surfactant protein-A (SP-A). Our studies set out to determine the contribution of SP-A to the response of a key effector cytokine in asthma, IL-13. Our studies employ both animal models sufficient and deficient in SP-A challenged with IL-13 and primary epithelial cells from participants with asthma that are exogenously treated with SP-A in the context of IL-13 challenge. The inflammatory response and mucin production were assessed in both model systems. As compared with WT mice, we show that the activity of IL-13 is dramatically augmented in SP-A2/2 mice, which have significantly increased neutrophil and eosinophil recruitment, mucin production and asthma-associated cytokines in the bronchoalveolar lavage fluid. In parallel, we show asthma-associated factors are attenuated in human cells from asthma subjects when exogenous SP-A is added during IL-13 challenge. Although many of these phenotypes have previously been associated with STAT6 signaling, SP-A inhibited IL-13-induced STAT3 phosphorylation in mice and in human epithelial cells while having little effect on STAT6 phosphorylation. In addition, when either STAT3 or IL-6 were inhibited in mice, the phenotypes observed in SP-A2/2 mice were significantly attenuated. These studies suggest a novel mechanism for SP-A in asthma as a modulator of IL-13-induced inflammation via mediating downstream IL-6/STAT3 signaling.

Original languageEnglish (US)
Pages (from-to)2829-2839
Number of pages11
JournalJournal of Immunology
Volume204
Issue number10
DOIs
StatePublished - May 15 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Francisco, D., Wang, Y., Conway, M., Hurbon, A. N., Dy, A. B. C., Addison, K. J., Chu, H. W., Voelker, D. R., Ledford, J. G., & Kraft, M. (2020). Surfactant protein-A protects against IL-13–induced inflammation in asthma. Journal of Immunology, 204(10), 2829-2839. https://doi.org/10.4049/jimmunol.1901227