γ-glutamylcysteine (GGC) supplementation and p-LPS challenge causes distinct proteomic changes to primary airway epithelial cell models of Cystic Fibrosis

Cystic fibrosis (CF) is a life limiting inherited condition associated with recurrent bacterial infections, inflammation, oxidative stress and loss of lung function. CF is characterised by deficiencies in both intra- and extracellular glutathione (GSH) levels. This GSH depletion is exacerbated by bacterial infections which further contributes to cellular oxidative stress and the inadequate control of inflammatory pathways in CF patients. A considerable body of research supports targeting the GSH biosynthesis pathway as a therapeutic strategy, however, current therapies have not demonstrated relevant improvements in CF clinical outcomes. It has previously shown that the immediate pre-cursor to glutathione, γ-glutamylcysteine (GGC) is effective in increasing intracellular levels of GSH in vivo in healthy humans. In this in-vitro primary cell line study, we study the proteomic changes involved in treating airway epithelial cells with GGC both prior to and post-LPS challenge, and without LPS challenge.