C1P in CS induced lung inflammation

Abstract

Sphingolipids are playing an essential role in normal cell and 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. Several studies now suggest that C1P are likely to have an integral role in inflammation. C1P has been shown to play an important role in regulating cell proliferation and apoptosis. In addition, recent studies revealed that C1P is also a mediator of inflammatory responses. We therefore investigated the in vivo anti-inflammatory effects of C1P and we focussed on their potential role and impact in the filed of chronic obstructive pulmonary disease(COPD). Here, we show that C1P suppresses production of pro-inflammatory cytokines. The role of C1P will be analysed in COPD driven model of cigarette smoke (CS) induced lung inflammation. The acute and chronic smoke models were studied in C57/BL6 mice (6–8 weeks old). Mice have got the treatment (C1P 10µM) 30 minutes before we induced a CS lung inflammation. BALF was collected and the number and distribution of different cells analysed by flow cytometer. The cytokine content was measured by Elisa. In summary, our studies suggest that C1P is involved in regulating of pro-inflammatory cytokines and has a role in the regulation of COPD and possibly other allergic diseases.