Knob protein enhances epithelial barrier integrity and attenuates airway inflammation

Publication date: Available online 6 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): 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
BackgroundAltered 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.ObjectiveTo determine the immunomodulatory effect of knob protein of the adenoviral capsid on allergic asthma and investigate its mechanism of action on airway epithelial junction proteins and barrier function.MethodsAirway inflammation including junction protein expression was evaluated in allergen-challenged mice with and without treatment with knob. Human bronchial epithelial cells (Hu-BEC) were exposed to knob and its effect on expression of junction proteins and barrier integrity were determined.ResultsAdministration of knob to allergen-challenged mice suppressed airway inflammation (eosinophilia, airway hyperresponsiveness, 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 Hu-BEC with knob activated JNK, increased expression of occludin and E-cadherin and enhanced epithelial barrier integrity.ConclusionIncreased expression of junction proteins mediated by knob leading to enhanced epithelial barrier function may mitigate allergen-induced airway inflammatory response including asthma.



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