RT Journal Article SR Electronic T1 Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 1669 OP 1680 DO 10.1183/09031936.00080014 VO 45 IS 6 A1 Kristin Baudiß A1 Cemil Korcan Ayata A1 Zsofia Lazar A1 Sanja Cicko A1 Jessica Beckert A1 Anja Meyer A1 Andreas Zech A1 Rodolfo Paula Vieira A1 Robert Bittman A1 Antonio Gómez-Muñoz A1 Irmgard Merfort A1 Marco Idzko YR 2015 UL http://erj.ersjournals.com/content/45/6/1669.abstract AB 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. Ceramide-1-phosphate, a potential target for anti-inflammatory treatment in cigarette smoke-induced lung inflammation http://ow.ly/E7tUS