Knob protein enhances epithelial barrier integrity and attenuates airway inflammation

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.

Asthma and Lung Mechanics

“…Similarly, epithelial cells exposed to mechanical compression equivalent to bronchoconstriction cause an endothelin-1 mediated increase in ASM contraction [149]. Lastly, damage to the airway epithelium is associated with an increase in inflammatory mediators, such as IL-33, which may contribute to AHR through exaggerated (eosinophilic) airway inflammation [89]. All the above mechanisms are likely especially relevant to the development of occupational asthma following inhalation of noxious molecules.…”

Robust and self-lubricating polyvinyl alcohol tubes with a mucosa-like hierarchical architecture for endotracheal intubation

“…56 E-Cadherin plays a crucial role in adhesion junctions, which are essential for cell attachment to epithelial tissues. 57 Studies have shown that inflammatory mediators, such as cytokines 58 and proteases, 59 influence the expression and activity of E-Cadherin, resulting in increased epithelial permeability and impaired airway barrier function. In the control group, E-Cadherin was uniformly distributed like a wall across the tracheal mucosa, and the E-Cadherin barriers in the PVA and Pristine PVA group remained complete.…”

“…56 E-Cadherin plays a crucial role in adhesion junctions, which are essential for cell attachment to epithelial tissues. 57 Studies have shown that inflammatory mediators, such as cytokines 58 and proteases, 59 influence the expression and activity of E-Cadherin, resulting in increased epithelial permeability and impaired airway barrier function.…”

Loss of PP4 contributes to diesel exhaust particles‐induced epithelial barrier integrity disruption and alarmins release

“…The barrier integrity and permeability were verified based on the transepithelial electric resistance (TER) and paracellular flux. 6 Loss of PP4 reduced TER (Figure S2C) and increased paracellular flux (Figure S2D) in a concentration-dependent manner, which suggested that PP4 exerted a protective effect on epithelial barrier function by maintaining baseline expression of TJ proteins.…”