Cigarette Smoke Modulates Repair and Innate Immunity following Injury to Airway Epithelial Cells

Abstract

Cigarette smoking is the main risk factor associated with chronic obstructive pulmonary disease (COPD), and contributes to COPD development and progression by causing epithelial injury and inflammation. Whereas it is known that cigarette smoke (CS) may affect the innate immune function of airway epithelial cells and epithelial repair, this has so far not been explored in an integrated design using mucociliary differentiated airway epithelial cells. In this study, we examined the effect of whole CS exposure on wound repair and the innate immune activity of mucociliary differentiated primary bronchial epithelial cells, upon injury induced by disruption of epithelial barrier integrity or by mechanical wounding. Upon mechanical injury CS caused a delayed recovery in the epithelial barrier integrity and wound closure. Furthermore CS enhanced innate immune responses, as demonstrated by increased expression of the antimicrobial protein RNase 7. These differential effects on epithelial repair and innate immunity were both mediated by CS-induced oxidative stress. Overall, our findings demonstrate modulation of wound repair and innate immune responses of injured airway epithelial cells that may contribute to COPD development and progression.

Transcriptomic and barrier responses of human airway epithelial cells exposed to cannabis smoke

“…To complement the mechanical barrier of the lung, the airway epithelium is able to produce and host‐defence peptides and antiviral mediators to protect from pathogens (Parker and Prince, ; Huff et al, ). Tobacco smoke has been reported to compromise the ability of airway epithelial cells to effectively control both bacterial and viral insults (Hudy et al, ; Eddleston et al, ; Rider et al, ; Amatngalim et al, ). Our data demonstrating striking similarities in the epithelial immune profile in response to cannabis and tobacco, suggests that the former will impact host defences.…”

“…Methods incorporating the use of smoke conditioned media have been used extensively for tobacco research (Wirtz and Schmidt, 1996;Bernhard et al, 2004;Bauer et al, 2008;Hudy et al, 2010;Hudy and Proud, 2013;Hudy et al, 2014;Amatngalim et al, 2016;Jamieson et al, 2019). Smoke conditioned media methods typically filter coarse particulates and extract water-soluble components of smoke combustion.…”

“…To address the above issues, we performed a series of in vitro functional and transcriptomic experiments with a human airway epithelial cell line (Calu‐3) exposed to cannabis smoke, with tobacco smoke used as a positive control. To model cannabis smoke exposure, we used smoke conditioned media methods that have been validated for tobacco combustion experiments (Wirtz and Schmidt, ; Bernhard et al, ; Bauer et al, ; Hudy et al, ; Hudy and Proud, ; Hudy et al, ; Amatngalim et al, ; Jamieson et al, ). Comparison of differential gene expression patterns from our tobacco smoke conditioned media experiments in Calu‐3 cells to bronchial brushings from human tobacco smokers (Harvey et al, ; Tilley et al, ) and air‐liquid interface cultures of primary epithelial cells exposed to mainstream tobacco smoke (Mathis et al, ; Haswell et al, ; Haswell et al, ) revealed overlap, validating the relevance of our model.…”

A comparative analysis of cannabis and tobacco smoke exposure on human airway epithelial cell gene expression, immune phenotype, and response to formoterol and budesonide treatment

“…In Canada, the majority of cannabis is consumed by combustion with 94 and 89% of participants reporting this method of delivery in the 2017 and 2018 Canadian Cannabis Surveys, respectively (2,3). The negative effects of tobacco smoke exposure on the lung and its airway epithelium are universally accepted (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). In comparison, the consequences of cannabis smoke exposure on lung health are less clear (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) and must receive additional attention to effectively inform public health policy, government regulations, and individual user practices.…”

“…If pathogens are capable of penetrating and overwhelming the defences provided by mucus and airway surface lining fluid, innate immune receptors on airway epithelial cells are poised to recognize molecular structures and trigger production and release of immune mediators. Despite this multi-tiered defence strategy, innate immune protection rendered by the airway epithelium can be compromised by tobacco smoke (4)(5)(6)(8)(9)(10)(11) leading to increased susceptibility to bacterial or viral infection and potential for host pathology. Whether cannabis smoke exposure similarly impacts airway epithelial cell function and immune profile relevant in pathogen defence remains to be determined.…”