Ceramides, the principal building blocks of all sphingolipids, have attracted the attention of many scientists around the world interested in developing treatments for cystic fibrosis, the most common genetic disease of Caucasians. Many years of fruitful research in this field have produced some fundamentally important, yet controversial results. Here, we aimed to summarize the current knowledge on the role of long- and very-long- chain ceramides, the most abundant species of ceramides in animal cells, in cystic fibrosis and other diseases. We also aim to explain the importance of the length of their side chain in the context of stability of transmembrane proteins through a concise synthesis of their biophysical chemistry, cell biology, and physiology. This review also addresses several remaining riddles in this field. Finally, we discuss the technical challenges associated with the analysis and quantification of ceramides. We provide the evaluation of the antibodies used for ceramide quantification and we demonstrate their lack of specificity. Results and discussion presented here will be of interest to anyone studying these enigmatic lipids.

• MeSH
• bronchiální astma metabolismus   MeSH
• ceramidy chemie   metabolismus   MeSH
• cystická fibróza metabolismus   MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Cystic fibrosis (CF) is the most common genetic disease in Caucasians. CF is manifested by abnormal accumulation of mucus in the lungs, which serves as fertile ground for the growth of microorganisms leading to recurrent infections and ultimately, lung failure. Mucus in CF patients consists of DNA from dead neutrophils as well as mucins produced by goblet cells. MUC5AC mucin leads to pathological plugging of the airways whereas MUC5B has a protective role against bacterial infection. Therefore, decreasing the level of MUC5AC while maintaining MUC5B intact would in principle be a desirable mucoregulatory treatment outcome. Fenretinide prevented the lipopolysaccharide-induced increase of MUC5AC gene expression, without affecting the level of MUC5B, in a lung goblet cell line. Additionally, fenretinide treatment reversed the pro-inflammatory imbalance of fatty acids by increasing docosahexaenoic acid and decreasing the levels of arachidonic acid in a lung epithelial cell line and primary leukocytes derived from CF patients. Furthermore, for the first time we also demonstrate the effect of fenretinide on multiple unsaturated fatty acids, as well as differential effects on the levels of long- compared to very-long-chain saturated fatty acids which are important substrates of complex phospholipids. Finally, we demonstrate that pre-treating mice with fenretinide in a chronic model of P. aeruginosa lung infection efficiently decreases the accumulation of mucus. These findings suggest that fenretinide may offer a new approach to therapeutic modulation of pathological mucus production in CF.

• MeSH
• aplikace orální MeSH
• buněčné linie MeSH
• cystická fibróza komplikace   genetika   patologie   MeSH
• fenretinid aplikace a dávkování   MeSH
• fosfolipidy metabolismus   MeSH
• hlen metabolismus   MeSH
• krysa rodu rattus MeSH
• kyselina arachidonová metabolismus   MeSH
• kyseliny dokosahexaenové metabolismus   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• mucin 5AC metabolismus   MeSH
• mucin 5B metabolismus   MeSH
• myši inbrední CFTR MeSH
• myši MeSH
• plíce účinky léků   metabolismus   patologie   MeSH
• pneumonie mikrobiologie   patologie   prevence a kontrola   MeSH
• pseudomonádové infekce mikrobiologie   patologie   prevence a kontrola   MeSH
• Pseudomonas aeruginosa patogenita   MeSH
• respirační sliznice cytologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH