C1P Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Preventing NF-κB Activation in Neutrophils.

Abstract

Recently, ceramide-1-phosphate (C1P) has been shown to modulate acute inflammatory events. Acute lung injury (Arnalich et al. 2000. Infect. Immun. 68: 1942-1945) is characterized by rapid alveolar injury, lung inflammation, induced cytokine production, neutrophil accumulation, and vascular leakage leading to lung edema. The aim of this study was to investigate the role of C1P during LPS-induced acute lung injury in mice. To evaluate the effect of C1P, we used a prophylactic and therapeutic LPS-induced ALI model in C57BL/6 male mice. Our studies revealed that intrapulmonary application of C1P before (prophylactic) or 24 h after (therapeutic) LPS instillation decreased neutrophil trafficking to the lung, proinflammatory cytokine levels in bronchoalveolar lavage, and alveolar capillary leakage. Mechanistically, C1P inhibited the LPS-triggered NF-κB levels in lung tissue in vivo. In addition, ex vivo experiments revealed that C1P also attenuates LPS-induced NF-κB phosphorylation and IL-8 production in human neutrophils. These results indicate C1P playing a role in dampening LPS-induced acute lung inflammation and suggest that C1P could be a valuable candidate for treatment of ALI.

• Authors: Kristin Baudiß, Rodolfo de Paula Vieira, Sanja Cicko, Korcan Ayata, Madelon Hossfeld, Nicolas Ehrat, Antonio Gómez-Muñoz, Holger K Eltzschig, Marco Idzko
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 196 Issue 5 Pg. 2319-26 (Mar 01 2016) ISSN: 1550-6606 [Electronic] United States
• PMID: 26800872 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 by The American Association of Immunologists, Inc.

Chemical References

• Ceramides
• Cytokines
• Interleukin-8
• Lipopolysaccharides
• NF-kappa B
• Transcription Factor RelA
• ceramide 1-phosphate

Topics

• Acute Lung Injury (drug therapy, etiology, metabolism, pathology)
• Animals
• Ceramides (metabolism, pharmacology)
• Cytokines (metabolism)
• Disease Models, Animal
• Gene Expression
• Humans
• Interleukin-8 (metabolism)
• Lipopolysaccharides (adverse effects)
• Male
• Mice
• NF-kappa B (genetics, metabolism)
• Neutrophils (drug effects, immunology, metabolism)
• Phosphorylation
• Transcription Factor RelA (metabolism)