Knob protein enhances epithelial barrier integrity and attenuates airway inflammation

Sung Gil Ha, Mythili Dileepan, Xiao Na Ge, Bit Na Kang, Yana G. Greenberg, Amrita Rao, Girija Muralidhar, Lali Medina-Kauwe, Michael A. Thompson, Christina M. Pabelick, Scott M. O'Grady, Savita P. Rao, P. Sriramarao

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background: Altered epithelial physical and functional barrier properties along with TH1/TH2 immune dysregulation are features of allergic asthma. Regulation of junction proteins to improve barrier function of airway epithelial cells has the potential for alleviation of allergic airway inflammation. Objective: We sought to determine the immunomodulatory effect of knob protein of the adenoviral capsid on allergic asthma and to investigate its mechanism of action on airway epithelial junction proteins and barrier function. Methods: Airway inflammation, including junction protein expression, was evaluated in allergen-challenged mice with and without treatment with knob. Human bronchial epithelial cells were exposed to knob, and its effects on expression of junction proteins and barrier integrity were determined. Results: Administration of knob to allergen-challenged mice suppressed airway inflammation (eosinophilia, airway hyperresponsiveness, and IL-5 levels) and prevented allergen-induced loss of airway epithelial occludin and E-cadherin expression. Additionally, knob decreased expression of TH2-promoting inflammatory mediators, specifically IL-33, by murine lung epithelial cells. At a cellular level, treatment of human bronchial epithelial cells with knob activated c-Jun N-terminal kinase, increased expression of occludin and E-cadherin, and enhanced epithelial barrier integrity. Conclusion: Increased expression of junction proteins mediated by knob leading to enhanced epithelial barrier function might mitigate the allergen-induced airway inflammatory response, including asthma.

Original languageEnglish (US)
Pages (from-to)1808-1817.e3
JournalJournal of Allergy and Clinical Immunology
Volume142
Issue number6
DOIs
StatePublished - Dec 2018

Keywords

  • E-cadherin
  • Knob protein
  • adenoviral capsid
  • airway epithelium
  • allergic airway inflammation
  • asthma
  • barrier integrity
  • occludin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Ha, S. G., Dileepan, M., Ge, X. N., Kang, B. N., Greenberg, Y. G., Rao, A., Muralidhar, G., Medina-Kauwe, L., Thompson, M. A., Pabelick, C. M., O'Grady, S. M., Rao, S. P., & Sriramarao, P. (2018). Knob protein enhances epithelial barrier integrity and attenuates airway inflammation. Journal of Allergy and Clinical Immunology, 142(6), 1808-1817.e3. https://doi.org/10.1016/j.jaci.2018.01.049