title: Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation.
abstract: Sphingolipids are involved in the pathogenesis of inflammatory diseases. The central molecule is ceramide, which can be converted into ceramide-1-phosphate (C1P). Although C1P can exert anti- and pro-inflammatory effects, its influence on cigarette smoke (CS)-induced lung inflammation is unknown. We aimed to clarify the role of C1P in the pathogenesis of CS-triggered pulmonary inflammation and emphysema in humans and mice. The effects of C1P were addressed on CS-induced lung inflammation in C57BL/6 mice, CS extract-triggered activation of human airway epithelial cells (AECs) and neutrophils from patients with chronic obstructive pulmonary disease. Differential cell counts in bronchoalveolar lavage fluid were determined by flow cytometry and pro-inflammatory cytokines were measured by ELISA. Expression and DNA binding of nuclear factor (NF)-κB and neutral sphingomyelinase (nSMase) were quantified by PCR, electrophoretic mobility shift and fluorometric assays. C1P reduced CS-induced acute and chronic lung inflammation and development of emphysema in mice, which was associated with a reduction in nSMase and NF-κB activity in the lungs. nSMase activity in human serum correlated negatively with forced expiratory volume in 1 s % predicted. In human AECs and neutrophils, C1P inhibited CS-induced activation of NF-κB and nSMase, and reduced pro-inflammatory cytokine release. Our results suggest that C1P is a potential target for anti-inflammatory treatment in CS-induced lung inflammation.
authors.affiliation: Dept of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Baudiß
authors.affiliation: Dept of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Cemil Korcan
authors.initials: CK
authors.lastname: Ayata
authors.affiliation: Dept of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Lazar
authors.affiliation: Dept of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Sanja
authors.initials: S
authors.lastname: Cicko
authors.affiliation: Dept of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Beckert
authors.affiliation: Dept of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Meyer
authors.affiliation: Dept of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zech
authors.affiliation: Dept of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Rodolfo Paula
authors.initials: RP
authors.lastname: Vieira
authors.affiliation: Dept of Chemistry and Biochemistry, Queens College, City University of New York, Flushing, NY, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bittman
authors.affiliation: Dept of Biochemistry and Molecular Biology, University of the Basque Country, Bilbao, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gómez-Muñoz
authors.affiliation: Dept of Pharmaceutical Biology and Biotechnology, Institute of Pharmaceutical Sciences, University of Freiburg, Freiburg, Germany.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Merfort
authors.affiliation: Dept of Pneumology, COPD and Asthma Research Group, University Hospital Freiburg, Freiburg, Germany. marco.idzko@uniklinik-freiburg.de.
authors.forename: Marco
authors.initials: M
authors.lastname: Idzko
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000473:pathology; D011656:Pulmonary Emphysema / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D012906:Smoke; D013108:Sphingomyelin Phosphodiesterase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014026:Nicotiana
chemical_list: D002518:Ceramides; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D012906:Smoke; C065576:ceramide 1-phosphate; D013108:Sphingomyelin Phosphodiesterase