Ceramide as a target in emphysema

Abstract

A feature of emphysema is the destruction of the walls of the airspaces in the bronchioles. Ceramide is a membrane sphingolipid that induces apoptosis. In lung samples from human emphysema, ceramide levels were much higher than in lungs from patients without emphysema. Emphysema can be induced in rats or mice with the vascular endothelial growth factor receptor antagonist SU5416, and this is associated with increased levels of ceramide. Fumonisin B1 is a specific inhibitor of dihydroceramide synthase. Fumonisin B1 inhibited the production of ceramide in response to SU5416, and reduced the SU5418-induced increase in alveolar diameter and number of severely damaged distal airspaces. A synthetic short-chain ceramide, C₁₂ ceramide instilled into the trachea of mice increased lung ceramide levels, and induced alveolar cell apoptosis and septal destruction. These results suggest that ceramide is a target in emphysema, and ways of reducing the effects of ceramide in the lung need to be investigated.

Keywords::

• apoptosis
• ceramide
• emphysema
• fumonisin B1
• VEGFR antagonist SU5416