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J Immunol. 2016 Mar 1;196(5):2319-26. doi: 10.4049/jimmunol.1402681. Epub 2016 Jan 22.

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

Author information

1
Department of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, 79106 Freiburg, Germany;
2
Department of Biochemistry and Molecular Biology, University of the Basque Country, 48080 Bilbao, Spain; and.
3
Organ Protection Program, Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045.
4
Department of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, 79106 Freiburg, Germany; marco.idzko@uniklinik-freiburg.de.

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.

PMID:
26800872
PMCID:
PMC4820392
[Available on 2017-03-01]
DOI:
10.4049/jimmunol.1402681
[Indexed for MEDLINE]
Free PMC Article

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