S100b expression in and effects on microglia

Abstract

We evaluated the intracellular and extracellular biological role of S100B protein with respect to microglia. S100B, which belongs to the multigenic family of Ca2+-binding proteins, is abundant in astrocytes where it is found diffusely in the cytoplasm and is associated with membranes and cytoskeleton constituents. S100B protein is also secreted by astrocytes and acts on these cells to stimulate nitric oxide secretion in an autocrine manner. However, little is known about the relationship between S100B and microglia. To address this issue, we used primary microglia from newborn rat cortex and the BV-2 microglial cell line, a well-established cell model for the study of microglial properties. S100B expression was assessed by immunofluorescence in primary microglia and by RT-PCR, Western blotting, and immunofluorescence in BV-2 cells. S100B was found in microglia in the form of a filamentous network as well as diffusely in the cytoplasm and associated with intracellular membranes. S100B relocated around phagosomes during BV-2 phagocytosis of opsonized Cryptococcus neoformans. Furthermore, interferon-gamma (IFN-gamma) treatment caused cell shape changes and redistribution of S100B, and downregulation of S100B mRNA expression in BV-2 cells. Treatment of BV-2 cells with nanomolar to micromolar amounts of S100B resulted in increased IFN-gamma-induced expression of inducible nitric oxide synthase mRNA as well as nitric oxide secretion. Taken together, these data suggest a possible role for S100B in the accomplishment/regulation of microglial cell functions.

S100B Inhibition Reduces Behavioral and Pathologic Changes in Experimental Traumatic Brain Injury

“…Previous studies using primary microglia from newborn rat cortex or BV-2 microglial cell lines have demonstrated that micromolar to nanomolar concentrations of S100B cause IFNγ-induced expression of iNOS as well as NO secretion. 10,36 In contrast, our studies using BV2 and primary microglial cultures stimulated by LPS and/or IFNγ showed no effects of S100B on key markers of microglial activation, such as NO release or ROS production. Furthermore, it has been proposed that S100B may act through AGER and subsequently Toll-like receptors to induce inflammatory responses.…”

Enhanced Cerebral Expression of MCT1 and MCT2 in a Rat Ischemia Model Occurs in Activated Microglial Cells

“…To our knowledge, it is the first time that colocalization between a microglial and an astrocytic marker is observed in vivo. However, it has been reported earlier that primary microglial cell cultures as well as the BV-2 microglial cell line express S100b in vitro (Adami et al, 2001). As it appears associated with filamentous structures, it is purported that S100b protein might be involved in cytoskeleton remodeling in these cells.…”

Role of microglia in fungal infections of the central nervous system

“…33 For example, microglia expresses the S100B protein which surrounds the phagosome of opsonized Cryptococcus neoformans, which in the presence of IFN-g stimulates transcription of the inducible NO synthase gene resulting in increased secretion of NO. 34 These cells express a greater number of PRRs, including TLRs and MHC II, allowing for increased communication with other immune cells through the secretion of cytokines and chemokines. 35 Nucleotide binding oligomerization domains-like receptors on microglia stimulate the production of IL-1b and IL-18 which assist in the recruitment of neutrophils into the CNS infection site.…”