Ceramide-1-Phosphate attenuates cigarette smoke induced lung inflammation

Sphingolipids are playing an essential role in normal cell und tissue homeostasis as well as in the development and progress of various diseases and disorders. The central molecule in the sphingolipid metabolism is ceramide, which has been shown to regulate vital cellular functions such as apoptosis, cell growth, differentiation, and important disease pathomechanism in inflammation. An important metabolite of ceramide is Ceramide-1-Phosphate (C1P), which is generated through direct phosphorylation of ceramide by ceramide kinase. While the role of Shingosine-1-Phosphate in the pathogenesis of airway inflammation has been extensively studied, little is known about C1P. The aim of the current study was to elucidate the role of C1P in the pathogenesis of cigarette smoke (CS)-induced lung inflammation and lung emphysema in mice.

Thereby we could show for the first time that intrapulmonary application of C1P can suppress all cardinal features of acute CS-induced lung inflammation in vivo. Furthermore was also able to prevent the development of lung emphysema in a chronic model of CS induced lung inflammation. Mechanistically ceramide 1 phosphate inhibited the CS induced NF-kB activation in vitro and in vivo. In summary, our studies suggest that ceramide 1 phosphate may have a role in the limiting CS induced lung inflammation and lung emphysema.