Sphingosine Kinase-1 (SPHK1) promotes inflammation in infantile pneumonia by regulating NLRP3 inflammasome and SIRT1 expression

Abstract

Background. Infantile pneumonia is an acute inflammatory disorder of the lung caused by mycoplasma pneumonia. SPHK1 (sphingosine kinase-1) signaling pathway is involved in the process of inflammatory diseases. However, whether SphK1 regulates inflammatory responses in infantile pneumonia remains unclear. In this study, we investigated the role of SPHK1 in infantile pneumonia and its underlying mechanisms. Methods. Serum samples of 12 patients with infantile pneumonia and healthy controls were obtained from Hunan Children's Hospital. To induce pneumonia, mice were administrated with LPS (lipopolysaccharide) into the lung. RAW264.7 cells were used as an in vitro macrophage model stimulated with LPS or PBS for 4 h. Results. SPHK1 mRNA level and protein level in the LPS-treated mice and patients with infantile pneumonia were significantly increased. SPHK1 promoted inflammation and lung injury in mice with infantile pneumonia. The knockdown of SPHK1 expression inhibited inflammation and restrained lung injury in mice with infantile pneumonia. SPHK1 overexpression also exacerbated inflammation in RAW264.7 cells stimulated by LPS, and SPHK1 silencing reduced inflammatory responses. We further showed that SPHK1 induced NLRP3 (NLR Family Pyrin Domain Containing 3) activity by inhibiting SIRT1 expression. Conclusion. Our study demonstrated that SPHK1 promotes inflammation of infantile pneumonia by modulating NLRP3 inflammasome via the regulation of SIRT1 expression and mitochondrial permeability transition