Possible roles of long-chain sphingomyelines and sphingomyelin synthase 2 in mouse macrophage inflammatory response.
To evaluate the precise role of sphingomyelin synthase 2 (SMS2) in sphingomyelin (SM) metabolism and their anti-inflammatory properties, we analyzed species of major SM and ceramide (Cer) (18:1, 18:0 sphingoid backbone, C14 - C26 N-acyl part) in SMS2 knockout and wild-type mouse plasma and liver using HPLC-MS. SMS2 deficiency significantly decreased very long chain SM (SM (d18:1/22:0) and SM (d18:1/24:0 or d18:0/24:1)) and increased very long chain Cer (Cer (d18:1/24:0 or d18:0/24:1) and Cer (d18:1/24:1)), but not long chain SM (SM (d18:1/16:0), SM (d18:1/18:0 or d18:0/18:1) and SM (d18:1/18:1)) in plasma. To examine the effects of SM on inflammation, we studied the role of very long chain SM in macrophage activation. Addition of SM (d18:1/24:0) strongly upregulated several macrophage activation markers, SM (d18:1/6:0) and Cer (d18:1/24:0) however, did not. It was suggested that very long chain SM but not long chain SM were decreased in SMS2-deficient mice liver and plasma. And the exogenously added very long chain SM (d18:1/24:0) could activate macrophages directly, suggesting a novel role of plasma very long chain SM in modulating macrophage activation and resulting inflammation.
Shionogi Innovation Center for Drug Discovery, Shionogi & Co., Ltd., Sapporo, Japan. Electronic address: hideaki.sakamoto@shionogi.co.jp.
Hideaki
H
Sakamoto
Shionogi Innovation Center for Drug Discovery, Shionogi & Co., Ltd., Sapporo, Japan.
Tetsuya
T
Yoshida
Research Laboratory for Development, Shionogi & Co., Ltd., Osaka, Japan.
Takao
T
Sanaki
Research Laboratory for Development, Shionogi & Co., Ltd., Osaka, Japan.
Shuhei
S
Shigaki
Research Laboratory for Development, Shionogi & Co., Ltd., Osaka, Japan.
Hirotoshi
H
Morita
Shionogi Innovation Center for Drug Discovery, Shionogi & Co., Ltd., Sapporo, Japan.
Miki
M
Oyama
Shionogi Innovation Center for Drug Discovery, Shionogi & Co., Ltd., Sapporo, Japan.
Masaru
M
Mitsui
Shionogi Innovation Center for Drug Discovery, Shionogi & Co., Ltd., Sapporo, Japan.
Yoshikazu
Y
Tanaka
Shionogi Innovation Center for Drug Discovery, Shionogi & Co., Ltd., Sapporo, Japan.
Toru
T
Nakano
Laboratory of Biomembrane and Biofunctional Chemistry, Graduate School of Advanced Life Science and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
Susumu
S
Mitsutake
Laboratory of Biomembrane and Biofunctional Chemistry, Graduate School of Advanced Life Science and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
Yasuyuki
Y
Igarashi
Shionogi Innovation Center for Drug Discovery, Shionogi & Co., Ltd., Sapporo, Japan.
Hiroshi
H
Takemoto
D000818:Animals; D002478:Cells, Cultured; D007155:Immunologic Factors / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008970:Molecular Weight; D013109:Sphingomyelins / Q000737:chemistry / Q000276:immunology*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000276:immunology*
D007155:Immunologic Factors; D018836:Inflammation Mediators; D013109:Sphingomyelins; D017855:Transferases (Other Substituted Phosphate Groups); C543123:Sgms2 protein, mouse
Inflammation; Long-chain sphingomyelin; Sphingomyelin synthase 2