Mechanism of glial activation by S100B: Involvement of the transcription factor NFκB

Amy G.M. Lam, Tanuja Koppal, Keith T. Akama, Ling Guo, Jeffrey M. Craft, Barat Samy, James P. Schavocky, D. Martin Watterson, Linda J. Van Eldik

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


Compelling evidence links chronic activation of glia and the subsequent cycle of neuroinflammation and neuronal dysfunction to the progression of neurodegeneration in disorders such as Alzheimer's disease (AD). S100B, a glial-derived cytokine, is significantly elevated in the brains of AD patients and high concentrations of S100B are believed to be detrimental to brain function. As a first step toward elucidating the mechanisms by which S100B might be serving this detrimental role, we examined the mechanisms by which S100B stimulates glial inducible nitric oxide synthase (iNOS), an oxidative stress related enzyme that has been linked to neuropathology through the production of neurotoxic peroxynitrite. We report here that S100B stimulates iNOS in rat primary cortical astrocytes through a signal transduction pathway that involves activation of the transcription factor NFκB. NFκB activation was demonstrated by nuclear translocation of the p65 NFκB subunit, stimulation of NFκB-specific DNA binding activity, and stimulation of NFκB-dependent transcriptional activity. Furthermore, S100B-induced iNOS promoter activation was inhibited upon mutation of the NFκB response element in the promoter, and transfection of cells with an NFκB inhibitor blocked S100B-induced iNOS promoter activation and nitric oxide production. These studies define a signal transduction pathway by which S100B activation of glia could participate in the generation of oxidative stress in the brain.

Original languageEnglish
Pages (from-to)765-772
Number of pages8
JournalNeurobiology of Aging
Issue number5
StatePublished - 2001

Bibliographical note

Funding Information:
This work was supported by a grant from the Alzheimer’s Association (to DMW), NIH grant AG13939 (to LVE), and NIH training grants AG00260 (to TK), GM08061 (to KTA), and GM08152 (to JMC). We thank Dr. Thomas Lukas for assistance with the amino acid analyses.


  • Alzheimer's disease
  • Astrocyte
  • Cytokine
  • Glia
  • NFκB
  • Nitric oxide
  • S100B
  • iNOS

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


Dive into the research topics of 'Mechanism of glial activation by S100B: Involvement of the transcription factor NFκB'. Together they form a unique fingerprint.

Cite this