Role of Sphingosine-1-phosphate pathway in Bisphenol A-induced inflammatory response in airway epithelial cells

The impact of environmental exposure to chemicals and their immunological effects, including the development of allergy, has becoming a topic of interest. Epidemiologic studies indicate that exposure to endocrine-disrupting chemicals, including bisphenol A (BPA) and phthalates, is ubiquitous. Prenatal and childhood exposure to these synthetic chemicals, have been linked to asthma and allergy, but the underlying mechanisms are not fully understood. In this context lipid metabolites such sphingolipids play an essential role. Here we investigated the contribute of sphingosine-1-phosphate pathway in BPA-induced effect on pulmonary epithelial cells. Human type II alveolar epithelial A549 cells were exposed for 24h to BPA (0,1-1μM). Cell viability was evaluated through MTT assay. Reactive oxidant species were measured by ROS assay. Expression of ORMDL3, ASAH1, NFkB, COX-2, Vimentin and alfa-SMA was evaluated with western blot or immunofluorescence (IF) analyses. BPA induced an increase in ORMDL3 and decrease in ASAH1 expression, suggesting BPA effect on sphingolipids pathway. A concomitant increase of COX-2 and decrease of NFkB occurred following BPA exposure. All this was coupled to a significant cellular production of reactive oxidant species, that underlined cellular inflammation and damage caused by BPA. This inflammatory effect was accompanied also by an induction of epithelial cells transition into mesenchymal cells as demonstrated by an increase in Vimentin and α-SMA expression. In conclusion data demonstrate that BPA induces lung epithelial damage and inflammation promoting sphingolipids pathway activation.