Modulation of glial activation by astrocyte-derived protein S100B: Differential responses of astrocyte and microglial cultures

Tatiana V. Petrova, Jingru Hu, Linda J. Van Eldik

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


The astrocyte-derived protein S100B stimulates production of inducible nitric oxide synthase and nitric oxide (NO) in astrocytes [Hu et al., 1996, J. Biol. Chem. 271:2543], but its effect on microglia is not known. In addition, S100B's ability to modulate the activity of other glial activating agents has not been defined. In this study, we compared the ability of S100B to stimulate NO in cultures of rat primary astrocytes and the BV-2 murine microglial cell line, and investigated the effect of the combined action of S100B and other stimuli known to activate glial cells. S100B itself stimulated the production of NO in astrocytes, and did not modify or potentiated only weakly the NO production induced by interleukin-1 beta, tumor necrosis factor alpha, dibutyryl cyclic AMP, zymosan A or lipid A. In contrast, S100B alone did not induce NO in BV-2 cells but strongly potentiated NO production in the presence of lipid A but not zymosan A. The deletion of eight C-terminal amino acid residues in S100B leads to a loss of the effect of S100B on microglia but not on astrocytes. These results demonstrate that responses of glial cells to extracellular S100B can vary depending on the cell type, and suggest that different structural features of S100B are important for the protein's effects on microglia and astrocytes. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)74-80
Number of pages7
JournalBrain Research
Issue number1
StatePublished - Jan 17 2000

Bibliographical note

Funding Information:
This work was supported in part by NIH grant AG13939 (L.V.E.), and by a postdoctoral fellowship from the Swiss National Science Foundation (T.P.). We thank E. Herbert for the production of S100B83stop mutant and L. Guo for assistance with the astrocyte cultures. We are grateful to Dr. Terry Ulrich of Ribi ImmunoChem Research (Hamilton, MT) for the gift of lipid A and lipid A derivatives.


  • Astrocyte
  • Cytokine
  • Microglia
  • Nitric oxide
  • S100
  • Site-directed mutagenesis

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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