Ceramides are an emerging class of anti-inflammatory
lipids, and nanoscale
ceramide-delivery systems are potential therapeutic strategies for inflammatory diseases. This study investigated the
therapeutic effects of
ceramide nanoliposomes (CNL) on type 2
inflammation-based
asthma, induced by repeated
ovalbumin (OVA) challenges. Asthmatic mice intratracheally treated with
ceramide-free
liposomes (Ghost) displayed typical
airway remodeling including mucosal accumulation and subepithelial
fibrosis, whereas, in CNL-treated mice, the degree of
airway remodeling was significantly decreased. Compared to the Ghost group, CNL treatment unexpectedly failed to significantly influence formation of type 2
cytokines, including
IL-5 and
IL-13, known to facilitate pathogenic production of airway mucus predominantly comprising MUC5AC
mucin. Interestingly, CNL treatment suppressed OVA-evoked
hyperplasia of MUC5AC-generating goblet cells in the airways. This suggests that CNL suppressed goblet cell
hyperplasia and airway mucosal accumulation independently of type 2
cytokine formation. Mechanistically, CNL treatment suppressed cell growth and
EGF-induced activation of Akt, but not ERK1/2, in a human lung epithelial cell culture system recapitulating airway goblet cell
hyperplasia. Taken together, CNL is suggested to have
therapeutic effects on
airway remodeling in allergic
asthma by targeting goblet cell
hyperplasia. These findings raise the potential of
ceramide-based
therapies for airway diseases, such as
asthma.