Tumor necrosis factor-alpha (TNF-α) regulates Toll-like receptor 2 (TLR2) expression in microglia
Version of Record online: 17 JUL 2007
Journal of Neurochemistry
Volume 103, Issue 4, pages 1461–1471, November 2007
How to Cite
Syed, M. Md., Phulwani, N. K. and Kielian, T. (2007), Tumor necrosis factor-alpha (TNF-α) regulates Toll-like receptor 2 (TLR2) expression in microglia. Journal of Neurochemistry, 103: 1461–1471. doi: 10.1111/j.1471-4159.2007.04838.x
- Issue online: 17 JUL 2007
- Version of Record online: 17 JUL 2007
- Received April 25, 2007; revised manuscript received June 22, 2007; accepted July 3, 2007.
- nuclear factor-kappa B;
- Toll-like receptor 2;
- tumor necrosis factor-alpha
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.