Document Detail

IKK NBD peptide inhibits LPS induced pulmonary inflammation and alters sphingolipid metabolism in a murine model.
MedLine Citation:
PMID:  22469869     Owner:  NLM     Status:  Publisher    
Airway epithelial NF-κB is a key regulator of host defence in bacterial infections and has recently evolved as a target for therapeutical approaches. Evidence is accumulating that ceramide, generated by acid sphingomyelinase (aSMase), and sphingosine-1-phosphate (S1-P) are important mediators in host defence as well as in pathologic processes of acute lung injury. Little is known about the regulatory mechanisms of pulmonary sphingolipid metabolism in bacterial infections of the lung. The objective of this study was to evaluate the influence of NF-κB on sphingolipid metabolism in Pseudomonas aeruginosa LPS-induced pulmonary inflammation. In a murine acute lung injury model with intranasal Pseudomonas aeruginosa LPS we investigated TNF-α, KC (murine IL-8), IL-6, MCP-1 and neutrophilic infiltration next to aSMase activity and ceramide and S1-P lung tissue concentrations. Airway epithelial NF-κB was inhibited by topically applied IKK NBD, a cell penetrating NEMO binding peptide. This treatment resulted in significantly reduced inflammation and suppression of aSMase activity along with decreased ceramide and S1-P tissue concentrations down to levels observed in healthy animals. In conclusion our results confirm that changes in sphingolipid metabolim due to Pseudomonas aeruginosa LPS inhalation are regulated by NF-κB translocation. This confirms the critical role of airway epithelial NF-κB pathway for the inflammatory response to bacterial pathogens and underlines the impact of sphingolipids in inflammatory host defence mechanisms.
Philipp von Bismarck; Supandi Winoto-Mohrbach; Mona Herzberg; Ulrike Uhlig; Stefan Schütze; Ralph Lucius; Martin F Krause
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-24
Journal Detail:
Title:  Pulmonary pharmacology & therapeutics     Volume:  -     ISSN:  1522-9629     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-4-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9715279     Medline TA:  Pulm Pharmacol Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Department of Paediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany.
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