Tumor necrosis factor-alpha (TNF-α) regulates Toll-like receptor 2 (TLR2) expression in microglia

Mohsin Md Syed, Nirmal K. Phulwani, Tammy Kielian

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Microglia represent one effector arm of CNS innate immunity as evident by their role in pathogen recognition. We previously reported that exposure of microglia to Staphylococcus aureus (S. aureus), a prevalent CNS pathogen, led to elevated Toll-like receptor 2 (TLR2) expression, a pattern recognition receptor capable of recognizing conserved structural motifs associated with gram-positive bacteria such as S. aureus. In this study, we demonstrate that the proinflammatory cytokine tumor necrosis factor-α (TNF-α) enhances TLR2 expression in microglia, whereas interleukin-1β has no significant effect. To determine the downstream signaling events responsible for elevated microglial TLR2 expression in response to TNF-α, a series of signal transduction inhibitors were employed. Treatment with caffeic acid phenethyl ester, an inhibitor of redox-mediated nuclear factor-kappa B activation, significantly attenuated TNF-α-induced TLR2 expression. Similar results were observed with the IKK-2 and IκB-α inhibitors SC-514 and BAY 11-7082, respectively. In contrast, no significant alterations in TLR2 expression were observed with protein kinase C or p38 mitogen-activated protein kinase inhibitors. A definitive role for TNF-α was demonstrated by the inability of S. aureus to augment TLR2 expression in microglia isolated from TNF-α knockout mice. In addition, TLR2 expression was significantly attenuated in brain abscesses of TNF-α knockout mice. Collectively, these results indicate that in response to S. aureus, TNF-α acts in an autocrine/paracrine manner to enhance TLR2 expression in microglia and that this effect is mediated, in part, by activation of the nuclear factor-kappa B pathway.

Original languageEnglish (US)
Pages (from-to)1461-1471
Number of pages11
JournalJournal of Neurochemistry
Issue number4
StatePublished - Nov 2007
Externally publishedYes


  • Microglia
  • Nuclear factor-kappa B
  • Toll-like receptor 2
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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