Modulation of microglial activity by salt load and SGK1.

Microglial cells are derived from myelogenous cells and their chronic activation elicits brain inflammation, which influences neurological activity. Comprehensive understanding of the regulation of microglial activation could therefore contribute to overcoming neuropsychiatric disorders. Recently, the importance of serum- and glucocorticoid-inducible kinases (SGKs) has been explored in immune cells such as T cells, dendritic cells and macrophages. We have already shown that SGK1 and SGK3 are expressed in microglial cells and associated with the regulation of lipopolysaccharide (LPS)-induced inflammatory molecules. Here we investigate whether salt load influences expression of SGK1 and inflammatory responses in murine primary microglia and an immortalized microglial cell line, BV-2. Additional amounts of NaCl were administrated and immunoblotting was carried out, and SGK1 was induced in dose- and time-dependent manners. Next, the dynamics of inflammatory mediators iNOS and TNF alpha were investigated by administration of LPS. iNOS mRNA was induced by LPS application and enhanced by NaCl preload. In support of these results, nitric oxide was produced by LPS and accelerated by NaCl preload. In contrast, however, NaCl preload reduced the release of TNF alpha, suggesting the modulation of immune responses by salt load. The effects of salt load on both cases were attenuated in SGK1-deleted cells. Taken together, these results indicate that salt load modulates inflammatory responses and that SGK1 assists salt load-induced inflammatory responses.