A multi-organ, lung-derived inflammatory response following in vitro airway exposure to cigarette smoke and next-generation nicotine delivery products.

Despite increasing use of in vitro models that closely resemble in vivo human biology, their application in understanding downstream effects of airway toxicity, such as inflammation, are at an early stage. In this study, we used various assays to examine the inflammatory response induced in MucilAir™ tissues and A549 cells exposed to three products known to induce toxicity. Reduced barrier integrity was observed in tissues following exposure to each product, with reduced viability and increased cytotoxicity also shown. Similar changes in viability were also observed in A549 cells. Furthermore, whole cigarette smoke (CS) induced downstream phenotypic THP-1 changes and endothelial cell adhesion, an early marker of atherosclerosis. In contrast, exposure to next-generation delivery product (NGP) aerosol did not induce this response. Cytokine, histological and RNA analysis highlighted increased biomarkers linked to inflammatory pathways and immune cell differentiation following exposure to whole cigarette smoke, including GM-CSF, IL-1β, cleaved caspase-3 and cytochrome P450 enzymes. As a result of similar observations in human airway inflammation, we propose that our exposure platform could act as a representative model for studying such events in vitro. Furthermore, this model could be used to test the inflammatory or anti-inflammatory impact posed by inhaled compounds delivered to the lung.