S100B proteins that lack one or both cysteine residues can induce inflammatory responses in astrocytes and microglia

Tanuja Koppal, Amy G.M. Lam, Ling Guo, Linda J. Van Eldik

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


The astrocytic protein S100B stimulates neurite outgrowth and neuronal survival during CNS development. S100B can also stimulate glial activation, leading to induction of pro-inflammatory molecules like interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS). Although it is known that S100B's neurotrophic activity requires a disulfide-linked dimeric form of the protein, the structural features of S100B that are important for glial activation have not been defined. As an initial step towards understanding the structural features of S100B required for its action on glia and to determine if these features are different from those required for its action on neurons, we tested two mutants of S100B for their ability to activate glia. The C68VC84S mutant lacks S100B's two cysteine residues (cys68, cys84) and lacks neurotrophic activity (Winningham-Major et al., 1989, J. Cell Biol. 109 3063-3071), and the truncation mutant S100B83stop lacks the C-terminal nine residues (including cys84) that have been shown to be important for some S100B:target protein interactions. We report here that both C68VC84S and S100B83stop stimulate glial activation, as determined by induction of iNOS and IL-1β in rat primary astrocyte and microglial cultures. C68VC84S showed activation profiles similar to those of wild-type S100B, demonstrating that a disulfide-linked dimer is not required for glial activation. S100B83stop also stimulated both iNOS and IL-1β, although S100B83stop was significantly less effective than wild-type S100B in inducing iNOS. These results indicate that the C-terminal region of S100B is not required for glial activation; however, its presence may influence the degree of activation by the protein. Altogether, these studies demonstrate that the structural features required for S100B's neurotrophic activity are distinct from those affecting its glial activation activity.

Original languageEnglish
Pages (from-to)401-407
Number of pages7
JournalNeurochemistry International
Issue number5-6
StatePublished - 2001

Bibliographical note

Funding Information:
These studies were supported in part by NIH grants AG13939, AG15501, RR13810 and NIH training grant AG00260. We thank Rachel Dusek for her help with purifying the mutant S100B proteins and Dr Thomas Lukas for his help with the mass spectrometric and amino acid analyses.


  • Astrocyte
  • Inflammatory cytokine
  • Interleukin
  • Microglia
  • Nitric oxide synthase
  • S100

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology


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