Abstract
BackgroundHouse dust mite (HDM) inhalation can cause airway epithelial damage which is implicated in the process of airway inflammation in asthma. High mobility group box 1 (HMGB1) is critically required for cellular damage and apoptosis as an important endogenous danger signal. Recently, Clara cell 16KDa protein (CC16) has been identified to exert anti-inflammatory and immunomodulatory influence in various injury-related diseases model. However, little is known about its ability to protect against airway epithelial injury in allergic asthma. This study was aimed to clarify the protective roles of CC16 on airway epithelia in HDM-induced asthma and the regulation of HMGB1 by CC16.MethodsMice were sensitized and challenged by HDM extract and administrated intranasally with CC16 (5 μg/g or 10 μg/g) or saline in the challenged period. The BEAS-2B human airway epithelial cell line were cultured with CC16 or the control vehicle and then exposed to HDM. Knockdown or overexpression of HMGB1 was induced by cell transfection or intratracheal injection of recombinant adenovirus.ResultsCC16 treatment decreased airway inflammation and histological damage of airway epithelium dose-dependently in HDM-induced asthma model. Airway epithelia apoptosis upon HDM stimulation was noticeably abrogated by CC16 in vivo and in vitro. In addition, upregulation of HMGB1 expression and its related signaling were also detected under HDM conditions, while silencing HMGB1 significantly inhibited the apoptosis of BEAS-2B cells. Furthermore, the activity of HMGB1-mediated signaling was restrained after CC16 treatment whereas HMGB1 overexpression abolished the protective effect of CC16 on HDM-induced airway epithelia apoptosis.ConclusionsOur data confirm that CC16 attenuates HDM-mediated airway inflammation and damage via suppressing airway epithelial cell apoptosis in a HMGB1-dependent manner, suggesting the role of CC16 as a potential protective option for HDM-induced asthma.
Highlights
House dust mite (HDM) inhalation can cause airway epithelial damage which is implicated in the process of airway inflammation in asthma
Given that airway damage and inflammation participate in HDM-induced asthma as well, we proposed that Clara cell 16KDa protein (CC16) might serve as a helpful regimen to abrogate injured airway epithelium
CC16, we explored the role of High mobility group box 1 (HMGB1) as well as its potential signal pathway involved in HDM-mediated airway epithelial cell injury and apoptosis
Summary
House dust mite (HDM) inhalation can cause airway epithelial damage which is implicated in the process of airway inflammation in asthma. Little is known about its ability to protect against airway epithelial injury in allergic asthma. This study was aimed to clarify the protective roles of CC16 on airway epithelia in HDM-induced asthma and the regulation of HMGB1 by CC16. Aeroallergens from house dust mites (HDMs) such as Dermatophagoides pteronyssinus are the most prevalent sources of a range of allergens which are highly associated with allergic asthma (Zhang et al 2018). Upon allergen recognition, activated and damaged airway epithelia release a variety of proinflammatory cytokines and chemokines, eventually leading to asthma pathogenesis (Lambrecht et al 2019). HDM allergen challenge contributes to epithelial cells apoptosis, increased epithelium permeability and histological changes, which orchestrates airway injury
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