Early mechanistic events induced by low molecular weight polycyclic aromatic hydrocarbons in mouse lung epithelial cells: a role for eicosanoid signaling

Low molecular weight polycyclic aromatic hydrocarbons (LMW PAHs; <206.3 g/mol) are under regulated environmental contaminants (e.g., secondhand smoke) that lead to gap junction dysregulation, p38 MAPK activation, and increased mRNA production of inflammatory mediators, such as cytokines and cyclooxygenase (COX2), in lung epithelial cells. However, the early mechanisms involving lipid signaling through the arachidonic acid pathway and subsequent eicosanoid production leading to these downstream events are not known. Common human exposures are to mixtures of LMW PAH’s, thus C10 cells (a mouse lung epithelial cell line) were exposed to a representative binary PAH mixture, 1-methylanthracene (1-MeA) and fluoranthene (Flthn), for 30 min – 24 h with and without p38 and cytosolic phospholipase A2 (cPLA2) inhibitors. cPLA2 inhibition reversed PAH-induced phospho-p38 MAPK activation and gap junction dysregulation at 30 min. A significant biphasic increase of cPLA2 protein was observed at 30 ...