Airway epithelial cells exposed to wildfire smoke extract exhibit dysregulated autophagy and barrier dysfunction consistent with COPD

Abstract

BackgroundIndividuals with respiratory disease are being increasingly exposed to wildfire smoke as populations encroach further into forested regions and climate change continues to bring higher temperatures with lower rainfall. Frequent exposures have significant potential to accelerate conditions such as chronic obstructive pulmonary disease (COPD) which is characterised by an exaggerated inflammatory response to environmental stimuli. Here we employ models of human airway epithelium exposed to wildfire smoke-extract (WFSE) to examine modulation in airway epithelial cell (AEC) survival, fragility and barrier function.MethodsSubmerged cultures of small airway epithelial cells (SAEC) and differentiated air-liquid interface (ALI) cultures of primary bronchial AEC (bAEC) were treated for 1–24 h with 1–10% WFSE generated from plant species found in the Australian bushland. Autophagy (LC3-II and Sequestosome), apoptosis (Poly-(ADP)-Ribose Polymerase (PARP) cleavage) and tight junction proteins were measured using western blot. Barrier function was assessed via permeability of fluorescein tracers and measuring trans-epithelial electrical resistance. The production of IL-6 was assessed using ELISA.ResultsPrimary epithelial models exposed to WFSE exhibited a significant blockade in autophagy as evidenced by an increase in LC3-II coupled with a concomitant elevation in Sequestosome abundance. These exposures also induced significant PARP cleavage indicative of apoptotic changes. ALI cultures of bAEC treated with 5% WFSE demonstrated barrier dysfunction with significant increases in paracellular molecular permeability and ionic conductance, and a reduction in the abundance of the tight junction proteins ZO-1 and Claudin-1. These cultures also exhibited increased IL-6 secretion consistent with the aberrant and pro-inflammatory repair response observed in the COPD airways. Further, blocks in autophagy and barrier disruption were significantly elevated in response to WFSE in comparison to similar exposures with cigarette smoke-extract.ConclusionWFSE inhibits autophagic flux and induces barrier dysfunction in the airway epithelium. As autophagy is a central regulator of cellular repair, viability, and inflammation, targeting the block in autophagic flux may ameliorate the consequences of wildfire smoke-exposure for individuals with pre-existing respiratory conditions.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0945-2) contains supplementary material, which is available to authorized users.

Mechanisms of lung toxicity induced by biomass burning aerosols

“…In addition, an increase in inflammatory gene expression was observed in cells exposed to wood tar extract ( Table 1 and Additional file 1: Figure S6). Some in vitro studies on exposure to water-soluble extracts from collected biomass burning particles have also indicated that exposure induces onset of an inflammatory response similar to that observed in our study [4,28,43,44], while other studies have shown only a minor inflammatory response following exposure to biomass burning extracts [42,45,46]. The combined results from this study suggested that the inflammatory response was increased in both the in vivo and in vitro exposures.…”

Sustained Effects on Lung Function in Community Members Following Exposure to Hazardous PM2.5 Levels from Wildfire Smoke

“…Therefore, the present study showing an increase in obstructive pathology based on spirometry results suggests a model of increased acute inflammation and activation of the innate immune system from wildfire smoke that results in tissue remodeling and decreased lung function ( Figure 6). firefighters and in vitro studies reported increased IL-6, a contributor to inflammatory lung pathology [33,34], in response to wildfire or wildfire smoke extract, respectively [35,36]. The firefighters were assessed in the acute phase and found increased serum levels of IL-6, IL-8 and decreased IL-10, while the lung epithelial cultures presented with increased IL-6 production in addition to other markers of COPD including dysfunction of tight junctions.…”

Sustained Effects on Lung Function in Community Members Following Exposure to Hazardous PM2.5 Levels from Wildfire Smoke

“…The ILC2 are important sources of IL-13 (35) and have been linked to asthma, an obstructive lung pathology. Additionally, studies in both re ghters and in vitro studies reported increased IL-6, a contributor to in ammatory lung pathology (36,37), in response to wild re or wild re smoke extract, respectively (38,39). The re ghters were assessed in the acute phase and found increased serum levels of IL-6, IL-8 and decreased IL-10, while the lung epithelial cultures presented with increased IL-6 production in addition to other markers of COPD including dysfunction of tight junctions.…”