Yang Xue, Yan Jun, Feng Juan
Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University. Shenyang, Liaoning 110004, P.R. China.
Mol Med Rep. 2017 Jun;15(6):3555-3565. doi: 10.3892/mmr.2017.6441. Epub 2017 Apr 7.
The collectin surfactant protein‑A (SP‑A), a potent host defense molecule, is well recognized for its role in the maintenance of pulmonary homeostasis and the modulation of inflammatory responses. While previous studies have detected SP‑A in numerous extrapulmonary tissues, there is still a lack of information regarding its expression in central nervous system (CNS) and potential effects in neuroinflammatory diseases, such as multiple sclerosis (MS). The present study used experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS, to investigate the expression of SP‑A in the CNS at different stages of disease progression. In addition, in vitro experiments with lipopolysaccharide (LPS)‑stimulated human astrocytes and microglia were performed to investigate the potential role of SP‑A in the modulation of CNS inflammatory responses. The results of the present study demonstrated widespread distribution of SP‑A in the rat CNS, and also identified specific expression patterns of SP‑A at different stages of EAE. In vitro, the current study revealed that treatment of human astrocytes and microglia with LPS promoted SP‑A expression in a dose‑dependent manner. Furthermore, exogenous SP‑A protein significantly decreased Toll‑like receptor 4 and nuclear factor‑κB expression, and reduced interleukin‑1β and tumor necrosis factor‑α levels. The results of the current study indicate a potential role for SP‑A in the modulation of CNS inflammatory responses.
凝集素表面活性蛋白A(SP-A)是一种强大的宿主防御分子,其在维持肺内稳态和调节炎症反应中的作用已得到充分认可。虽然先前的研究在许多肺外组织中检测到了SP-A,但关于其在中枢神经系统(CNS)中的表达以及在神经炎症性疾病(如多发性硬化症(MS))中的潜在作用,仍缺乏相关信息。本研究使用实验性自身免疫性脑脊髓炎(EAE),这是MS最常用的动物模型,来研究疾病进展不同阶段CNS中SP-A的表达。此外,还进行了脂多糖(LPS)刺激的人星形胶质细胞和小胶质细胞的体外实验,以研究SP-A在调节CNS炎症反应中的潜在作用。本研究结果表明SP-A在大鼠CNS中广泛分布,并且还确定了EAE不同阶段SP-A的特定表达模式。在体外,本研究表明用LPS处理人星形胶质细胞和小胶质细胞可剂量依赖性地促进SP-A表达。此外,外源性SP-A蛋白显著降低Toll样受体4和核因子-κB的表达,并降低白细胞介素-1β和肿瘤坏死因子-α水平。本研究结果表明SP-A在调节CNS炎症反应中具有潜在作用。