105 : Expression of the strawberry notch 2 gene is altered in the murine brain following LPS-endotoxemia and viral infection

Abstract

Interleukin (IL-) 6 plays a key role in the host response to injury and infection in the central nervous system (CNS). We identified strawberry notch 2 (Sbno2) as an IL-6/gp130 cytokine-signalling target gene in murine astrocytes and microglia. Sbno2 is a mouse homologue of the Sno gene in Drosophila to shown modulate Notch signalling. However, the function of Sbno2 in mammals is not known. Here, we investigated the regulation of Sbno2 gene by different cytokines in cultured glial cells in vitro and in the murine brain during LPS-endotoxemia or following viral infection. In murine astrocytes, Sbno2 mRNA was up-regulated by hyper-IL6, OSM, LIF and IL-11 as well as by IL-1b and TNFa, whereas in C8-B4 microglia only hyper-IL6 increased Sbno2 gene expression. With the exception of LIF, these cytokines also significantly induced SOCS3 gene expression, which is a major IL-6/STAT3 regulated target gene. Following LPS-induced systemic inflammation, Sbno2 mRNA was highly increased in the brain compared with control levels. Upon West Nile virus infection, Sbno2 mRNA increased significantly in the brain to reach maximum levels on day 7 post-infection. Similarly, lymphocytic choriomeningitis virus infection led to increased levels of Sbno2 mRNA on day 7 and 8 post-infection. Elevated Sbno2 gene expression in these models was also accompanied by a significant increase in SOCS3 gene expression. In conclusion, (1) hyper-IL6 is a potent stimulus for Sbno2 gene expression in astrocytes and microglia, whereas all other tested cytokines alter Sbno2 gene expression in astrocytes only, suggesting a differential response of astrocytes versus microglia to various cytokines, and (2) Sbno2 mRNA is increased significantly in the murine CNS in LPS-induced inflammation as well as following viral infection suggesting a role for Sbno2 in the inflammatory response during host defence. Supported by NH & MRC grants 632754 and APP1047265 and Austrian Science Fund (FWF): J3081-B09.