Surfactant protein D attenuates sub-epithelial fibrosis in allergic airways disease through TGF-β

Hirohisa Ogawa, Julie G. Ledford, Sambuddho Mukherjee, Yoshinori Aono, Yasuhiko Nishioka, James J. Lee, Keisuke Izumi, John W. Hollingsworth

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background: Surfactant protein D (SP-D) can regulate both innate and adaptive immunity. Recently, SP-D has been shown to contribute to the pathogenesis of airway allergic inflammation and bleomycin-induced pulmonary fibrosis. However, in allergic airways disease, the role of SP-D in airway remodeling remains unknown. The objective of this study was to determine the contribution of functional SP-D in regulating sub-epithelial fibrosis in a mouse chronic house dust mite model of allergic airways disease. Methods: C57BL/6 wild-type (WT) and SP-D-/- mice (C57BL/6 background) were chronically challenged with house dust mite antigen (Dermatophagoides pteronyssinus, Dp). Studies with SP-D rescue and neutralization of TGF-β were conducted. Lung histopathology and the concentrations of collagen, growth factors, and cytokines present in the airspace and lung tissue were determined. Cultured eosinophils were stimulated by Dp in presence or absence of SP-D. Results: Dp-challenged SP-D-/- mice demonstrate increased sub-epithelial fibrosis, collagen production, eosinophil infiltration, TGF-β1, and IL-13 production, when compared to Dp-challenged WT mice. By immunohistology, we detected an increase in TGF-β1 and IL-13 positive eosinophils in SP-D-/- mice. Purified eosinophils stimulated with Dp produced TGF-β1 and IL-13, which was prevented by co-incubation with SP-D. Additionally, treatment of Dp challenged SP-D-/- mice with exogenous SP-D was able to rescue the phenotypes observed in SP-D-/- mice and neutralization of TGF-β1 reduced sub-epithelial fibrosis in Dp-challenged SP-D-/- mice. Conclusion: These data support a protective role for SP-D in the pathogenesis of sub-epithelial fibrosis in a mouse model of allergic inflammation through regulation of eosinophil-derived TGF-β.

Original languageEnglish (US)
Article number143
JournalRespiratory Research
Volume15
Issue number1
DOIs
StatePublished - Nov 29 2014
Externally publishedYes

Keywords

  • Airway remodeling
  • Asthma
  • Eosinophil
  • Fibrosis
  • Surfactant protein D
  • Transforming growth factor beta

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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  • Cite this

    Ogawa, H., Ledford, J. G., Mukherjee, S., Aono, Y., Nishioka, Y., Lee, J. J., Izumi, K., & Hollingsworth, J. W. (2014). Surfactant protein D attenuates sub-epithelial fibrosis in allergic airways disease through TGF-β. Respiratory Research, 15(1), [143]. https://doi.org/10.1186/s12931-014-0143-9