title: Lipopolysaccharide modulates astrocytic S100B secretion: a study in cerebrospinal fluid and astrocyte cultures from rats.
abstract: BACKGROUND
  Inflammatory responses in brain are primarily mediated by microglia, but growing evidence suggests a crucial importance of astrocytes. S100B, a calcium-binding protein secreted by astrocytes, has properties of a neurotrophic or an inflammatory cytokine. However, it is not known whether primary signals occurring during induction of an inflammatory response (e.g. lipopolysaccharide, LPS) directly modulate S100B.
  
  
  METHODS
  In this work, we evaluated whether S100B levels in cerebrospinal fluid (CSF) and serum of Wistar rats are affected by LPS administered by intraperitoneal (IP) or intracerebroventricular (ICV) injection, as well as whether primary astrocyte cultures respond directly to lipopolysaccharide.
  
  
  RESULTS
  Our data suggest that S100B secretion in brain tissue is stimulated rapidly and persistently (for at least 24 h) by ICV LPS administration. This increase in CSF S100B was transient when LPS was IP administered. In contrast to these S100B results, we observed an increase in in TNFα levels in serum, but not in CSF, after IP administration of LPS. In isolated astrocytes and in acute hippocampal slices, we observed a direct stimulation of S100B secretion by LPS at a concentration of 10 μg/mL. An involvement of TLR4 was confirmed by use of specific inhibitors. However, lower levels of LPS in astrocyte cultures were able to induce a decrease in S100B secretion after 24 h, without significant change in intracellular content of S100B. In addition, after 24 h exposure to LPS, we observed a decrease in astrocytic glutathione and an increase in astrocytic glial fibrillary acidic protein.
  
  
  CONCLUSIONS
  Together, these data contribute to the understanding of the effects of LPS on astrocytes, particularly on S100B secretion, and help us to interpret cerebrospinal fluid and serum changes for this protein in neuroinflammatory diseases. Moreover, non-brain S100B-expressing tissues may be differentially regulated, since LPS administration did not lead to increased serum levels of S100B.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, Porto Alegre, Brazil.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Guerra
authors.forename: Lucas S
authors.initials: LS
authors.lastname: Tortorelli
authors.forename: Fabiana
authors.initials: F
authors.lastname: Galland
authors.forename: Carollina
authors.initials: C
authors.lastname: Da Ré
authors.forename: Elisa
authors.initials: E
authors.lastname: Negri
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Engelke
authors.forename: Letícia
authors.initials: L
authors.lastname: Rodrigues
authors.forename: Marina C
authors.initials: MC
authors.lastname: Leite
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005978:Glutathione / Q000378:metabolism; D057967:Infusions, Intraventricular; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D014409:Tumor Necrosis Factor-alpha; D005978:Glutathione