PMID- 17961202
OWN - NLM
STAT- MEDLINE
DCOM- 20071213
LR  - 20211020
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 103
IP  - 4
DP  - 2007 Nov
TI  - Tumor necrosis factor-alpha (TNF-alpha) regulates Toll-like receptor 2 (TLR2) 
      expression in microglia.
PG  - 1461-71
AB  - 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-alpha (TNF-alpha) enhances TLR2 expression in 
      microglia, whereas interleukin-1beta has no significant effect. To determine the 
      downstream signaling events responsible for elevated microglial TLR2 expression 
      in response to TNF-alpha, 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-alpha-induced TLR2 expression. Similar results were observed with the IKK-2 
      and IkappaB-alpha 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-alpha was demonstrated by the inability of S. aureus to augment TLR2 
      expression in microglia isolated from TNF-alpha knockout mice. In addition, TLR2 
      expression was significantly attenuated in brain abscesses of TNF-alpha knockout 
      mice. Collectively, these results indicate that in response to S. aureus, 
      TNF-alpha 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.
FAU - Syed, Mohsin Md
AU  - Syed MM
AD  - Department of Neurobiology and Developmental Sciences, University of Arkansas for 
      Medical Sciences, Little Rock, Arkansas, USA.
FAU - Phulwani, Nirmal K
AU  - Phulwani NK
FAU - Kielian, Tammy
AU  - Kielian T
LA  - eng
GR  - S10 RR019395/RR/NCRR NIH HHS/United States
GR  - R01 MH065297-04/MH/NIMH NIH HHS/United States
GR  - R01 MH065297/MH/NIMH NIH HHS/United States
GR  - R01 NS055385-05A2/NS/NINDS NIH HHS/United States
GR  - S10 RR019395-01A1/RR/NCRR NIH HHS/United States
GR  - R01 MH65297/MH/NIMH NIH HHS/United States
GR  - S10 RR19395/RR/NCRR NIH HHS/United States
GR  - P30 NS047546-03/NS/NINDS NIH HHS/United States
GR  - NS055385/NS/NINDS NIH HHS/United States
GR  - P30 NS047546/NS/NINDS NIH HHS/United States
GR  - P30 NS047546-02/NS/NINDS NIH HHS/United States
GR  - P20 RR6460/RR/NCRR NIH HHS/United States
GR  - R01 NS055385/NS/NINDS NIH HHS/United States
GR  - P30 NS047546-04/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Gene Expression Regulation/*physiology
MH  - Inflammation Mediators/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microglia/*metabolism/microbiology
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Signal Transduction/physiology
MH  - Staphylococcus aureus/physiology
MH  - Toll-Like Receptor 2/*biosynthesis/genetics
MH  - Tumor Necrosis Factor-alpha/deficiency/genetics/*physiology
MH  - Up-Regulation/physiology
PMC - PMC2423670
MID - NIHMS48473
EDAT- 2007/10/27 09:00
MHDA- 2007/12/14 09:00
PMCR- 2008/06/10
CRDT- 2007/10/27 09:00
PHST- 2007/10/27 09:00 [pubmed]
PHST- 2007/12/14 09:00 [medline]
PHST- 2007/10/27 09:00 [entrez]
PHST- 2008/06/10 00:00 [pmc-release]
AID - JNC4838 [pii]
AID - 10.1111/j.1471-4159.2007.04838.x [doi]
PST - ppublish
SO  - J Neurochem. 2007 Nov;103(4):1461-71. doi: 10.1111/j.1471-4159.2007.04838.x.