title: 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.affiliation: Department of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, 79106 Freiburg, Germany;
authors.forename: Kristin
authors.initials: K
authors.lastname: Baudiß
authors.affiliation: Department of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, 79106 Freiburg, Germany;
authors.forename: Rodolfo
authors.initials: R
authors.lastname: de Paula Vieira
authors.affiliation: Department of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, 79106 Freiburg, Germany;
authors.forename: Sanja
authors.initials: S
authors.lastname: Cicko
authors.affiliation: Department of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, 79106 Freiburg, Germany;
authors.forename: Korcan
authors.identifier: http://orcid.org/0000-0001-7043-6692
authors.initials: K
authors.lastname: Ayata
authors.affiliation: Department of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, 79106 Freiburg, Germany;
authors.forename: Madelon
authors.initials: M
authors.lastname: Hossfeld
authors.affiliation: Department of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, 79106 Freiburg, Germany;
authors.forename: Nicolas
authors.identifier: http://orcid.org/0000-0002-9964-6367
authors.initials: N
authors.lastname: Ehrat
authors.affiliation: Department of Biochemistry and Molecular Biology, University of the Basque Country, 48080 Bilbao, Spain; and.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gómez-Muñoz
authors.affiliation: Organ Protection Program, Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045.
authors.forename: Holger K
authors.initials: HK
authors.lastname: Eltzschig
authors.affiliation: Department of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, 79106 Freiburg, Germany; marco.idzko@uniklinik-freiburg.de.
authors.forename: Marco
authors.initials: M
authors.lastname: Idzko
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002518:Ceramides / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010766:Phosphorylation; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D002518:Ceramides; D016207:Cytokines; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051996:Transcription Factor RelA; C065576:ceramide 1-phosphate