S100B modifies astroglial cell morphology, promotes migration and activates NF-kB in a dose- dependent manner

VILLARREAL A; SEOANE R; ANGELO F; AVILES R; ROSSI A; RAMOS AJ

Congreso; Society for Neuroscience Annual Meeting; 2011

S100B is a major constituent =f astrocytes cytoplasm and its secretion is increased under cell stress =onditions such as those produced by brain ischemia, hypoxia or traumatic brain =njury. Extracellular S100B has autocrine effects on astrocytes inducing cell proliferation and secretion of pro-inflammatory mediators. Most of the =100B effects are mediated by the Receptor for Advanced Glycated End Products =RAGE) which showed to induce NF-κB transcriptional activity in cell lines =nd primary neurons. By using rat primary astrocytes exposed to increasing S100B =evels, we show here that astroglial morphology is profoundly altered by S100B =xposure which increases the complexity of cell projections in filamentous =strocytes in the nanomolar range of concentration (up to 500 nM). This effect is =revented by RAGE-neutralizing antibodies. Scratch wound healing assays demonstrated =hat S100B stimulated astrocytes to extend membrane protrusions and to =igrate into the wounded areas, in a RAGE-dependent manner. S100B also promoted =F-κB nuclear localization in primary astrocytes and significantly activated a =FP-NF-κB reporter construct in a dose-dependent manner. Further, chemical =F-κB blockage with suphazalazine reduced the absolute number and complexity of glial =ell projections, an effect prevented by 1 μM, but not 10nM, S100B which =estored the cell morphology. Astrocytes exposed for 16h to nanomolar S100B also =mproved their survival to oxidative stress conditions induced by a subsequent 2 = exposure to hydrogen peroxide 200 μM. Together, these findings =uggest that astrocytes respond to extracellular S100B in a RAGE-dependent manner =ith morphological changes, alterations of their migratory capacity and =ctivation of NF-κB dependent transcription, all features that resemble reactive =liosis in vivo. These results support the hypothesis that S100B may behave as a Damage-Associated Molecular Pattern (DAMP) protein that promotes the =nitial phases of neuroinflammation by stimulating reactive gliosis.