Department of Respiratory Medicine, Hunan Children's Hospital, Changsha, Hunan Province, PR China.
College of Clinical Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, PR China.
Histol Histopathol. 2022 Dec;37(12):1227-1240. doi: 10.14670/HH-18-491. Epub 2022 Jul 7.
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.
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.
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.
Our study demonstrated that SPHK1 promotes inflammation of infantile pneumonia by modulating NLRP3 inflammasome via the regulation of SIRT1 expression and mitochondrial permeability transition.
小儿肺炎是由肺炎支原体引起的肺部急性炎症性疾病。SPHK1（鞘氨醇激酶-1）信号通路参与炎症性疾病的过程。然而，SphK1 是否调节小儿肺炎中的炎症反应尚不清楚。在这项研究中，我们研究了 SPHK1 在小儿肺炎中的作用及其潜在机制。
从湖南省儿童医院获得 12 例小儿肺炎患者和健康对照者的血清样本。通过向肺部给予 LPS（脂多糖）来诱导肺炎。将 RAW264.7 细胞用作体外巨噬细胞模型，用 LPS 或 PBS 刺激 4 小时。
LPS 处理的小鼠和患有小儿肺炎的患者的 SPHK1 mRNA 水平和蛋白水平均显着增加。SPHK1 促进了小儿肺炎小鼠的炎症和肺损伤。SPHK1 表达的敲低抑制了小儿肺炎小鼠的炎症并抑制了肺损伤。SPHK1 的过表达也加剧了 LPS 刺激的 RAW264.7 细胞中的炎症，而 SPHK1 沉默则减少了炎症反应。我们进一步表明，SPHK1 通过抑制 SIRT1 表达诱导 NLRP3（NLR 家族包含 pyrin 域的 3）活性。
我们的研究表明，SPHK1 通过调节 SIRT1 表达和线粒体通透性转换来调节 NLRP3 炎性小体，从而促进小儿肺炎的炎症。
