title: Sphingomyelin synthase 2 (SMS2) deficiency attenuates LPS-induced lung injury.
abstract: Sphingomyelin synthase (SMS) catalyzes the synthesis of sphingomyelin (SM) and is required for maintenance of plasma membrane microdomain fluidity. Of the two isoforms of mammalian SMS, SMS1 is mostly present in the trans-Golgi apparatus, whereas SMS2 is predominantly found at the plasma membrane. SMS2 has a role in receptor mediated response to inflammation in macrophages, however, the role of SMS2 in vascular permeability, pulmonary edema, and lung injury have not been investigated. To define the role of SMS activation in lung injury, we utilized a lipopolysaccharide (LPS)-induced lung edema model. SMS activity was measured and correlated with the severity of lung injury. Within 4 h of LPS treatment, SMS activity was increased significantly and remained upregulated up to 24 h. Comparison of LPS-induced lung injury in SMS2 knockout (SMS2(-/-)) and wild-type littermate control mice showed that inflammation, cytokine induction, and lung injury were significantly inhibited in SMS2(-/-) mice. Our results suggest that a deficiency of SMS2 can diminish the extent of pulmonary edema and lung injury. Furthermore, we show that depletion of SMS2 was sufficient to decrease MAP kinase-JNK activation, severity of LPS-induced pulmonary neutrophil influx, and inflammation, suggesting a novel role of SMS2 activation in lung injury.
authors.affiliation: SUNY Downstate and Veterans Affairs Medical Center, Brooklyn, New York, USA.
authors.forename: Satish
authors.initials: S
authors.lastname: Gowda
authors.forename: Calvin
authors.initials: C
authors.lastname: Yeang
authors.forename: Sunil
authors.initials: S
authors.lastname: Wadgaonkar
authors.forename: Fatima
authors.initials: F
authors.lastname: Anjum
authors.forename: Natalia
authors.initials: N
authors.lastname: Grinkina
authors.forename: Michael
authors.initials: M
authors.lastname: Cutaia
authors.forename: Xian-Chen
authors.initials: XC
authors.lastname: Jiang
authors.forename: Raj
authors.initials: R
authors.lastname: Wadgaonkar
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000201:enzymology / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000150:complications / Q000201:enzymology* / Q000473:pathology*; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011014:Pneumonia / Q000150:complications / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013109:Sphingomyelins / Q000096:biosynthesis; D013997:Time Factors; D014158:Transcription, Genetic; D017855:Transferases (Other Substituted Phosphate Groups) / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000199:Actins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D013109:Sphingomyelins; D014409:Tumor Necrosis Factor-alpha; D048055:Mitogen-Activated Protein Kinase 8; C556686:Sgms1 protein, mouse; D017855:Transferases (Other Substituted Phosphate Groups); C543123:Sgms2 protein, mouse