Abstract
Background
SNS-1 protein is known to play an important role in innate immune responses by inhibiting Gram-negative bacteria growth and mediating intestinal defense. SNS-1 gene expression increases in meningeal cells and glial cells after exposure to bacterial components. However, little is known about its functional role in the central nervous system (CNS).
Methods
The present study was undertaken to examine SNS-1 gene expression and functions in experimental autoimmune encephalomyelitis (EAE) and lipopolysaccharide (LPS)-induced neuroinflammation models. Mouse primary glial and splenocyte cultures were also employed for mechanistic studies. RT-PCR, immunohistochemistry analyses, and exogenous protein administration were performed to examine SNS-1 gene expression and functions.
Results
The expression of SNS-1 was found to be increased in spinal cords and brain during EAE progression and LPS-induced neuroinflammation. SNS-1 protein was expressed in Ly6G-positive neutrophils and Iba-1-positive microglial cells, but not neurons or astrocytes, after EAE induction. SNS-1 protein-injected mice exhibited accelerated onset time and increased EAE severity. The injection of SNS-1 protein enhanced glial cell activation in spinal cord of EAE-induced mice, whereas it reduced microglial activation in brain of LPS-injected mice. In the mechanistic studies using glial cells in culture, the expression of SNS-1 was enhanced by various inflammatory mediators. SNS-1 protein differentially regulated glial activation depending on inflammatory triggers: SNS-1 protein synergized with cytokines to induce inflammatory activation of glia, but antagonized LPS-induced responses. Furthermore, SNS-1 treatment augmented T helper cell-related Ifng gene expression in cultured splenocytes.
Conclusions
These results indicate that SNS-1 regulates inflammatory glial activation and neuroinflammation, and suggest that SNS-1 can be considered as a potential therapeutic target in multiple sclerosis and other inflammatory CNS disorders.
