Sphingomyelin synthase 2 affects CD14‑associated induction of NF‑κB by lipopolysaccharides in acute lung injury in mice

Hu,Shidong; Ding,Yi; Gong,Jie; Yan,Nianlong

doi:10.3892/mmr.2016.5611

Sphingomyelin synthase 2 affects CD14‑associated induction of NF‑κB by lipopolysaccharides in acute lung injury in mice

Authors:
- Shidong Hu
- Yi Ding
- Jie Gong
- Nianlong Yan
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Affiliations: Department of General Surgery, The General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China, Department of Graduate School, Nanchang University Health Science Center, Nanchang, Jiangxi 330006, P.R. China, Department of Anesthesiology, The General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China, Department of Biochemistry, College of Basic Medical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: August 9, 2016 https://doi.org/10.3892/mmr.2016.5611
Pages: 3301-3306

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Abstract

Lipopolysaccharide (LPS) is the predominant component of the outer membrane of Gram-negative bacteria, which can cause severe inflammation in the body. The acute lung injury (ALI) induced by LPS can cause extensive damage to the lung tissue, the severe stage of which is termed acute respiratory distress syndrome, when multiple organ dysfunction syndrome may appear. There are no effective clinical treatment measures at present. The involvement of cluster of differentiation (CD)14 assists LPS in causing inflammatory reactions, and CD14 and sphingomyelin (SM), located in lipid rafts areas, are closely associated. SM synthase (SMS) is a key enzyme in the synthesis of SM, however, the effect of SMS on the inflammatory pathway involving nuclear factor (NF)‑κB induced by LPS remains to be elucidated. Under the premise of the establishment of an ALI mouse model induced by LPS, the present study established a control group, LPS group and pyrrolidine dithiocarbamate (PDTC; an NF‑κB pathway inhibitor) group. Hematoxylin‑eosin staining, reverse transcription‑quantitative polymerase chain reaction analysis, western blot analysis and thin layer chromatography were used to investigate the mechanism of SMS in ALI. Compared with the control group, the mRNA and protein levels of CD14 were significantly increased (P<0.001; n=5 and P<0.05, n=5), and the activity of SMS and expression of SMS2 were significantly upregulated (P<0.001; n=5 and P<0.05, n=5) in the model group. The increases of SMS2 and CD14 in the PDTC group were less marked, compared with those in the model group (P<0.05; n=5). These findings suggested that the degree of lung injury was reduced during the acute inflammatory reaction when NF‑κB was inhibited, and that the expression of SMS2 may affect the induction of the NF‑κB pathway by LPS through CD14.

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