Inhibition of toll-like receptor signaling in primary murine microglia

Rajagopal N. Aravalli, Shuxian Hu, James R. Lokensgard

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Microglial cells respond to the herpes simplex virus (HSV)-1 by producing proinflammatory cytokines and chemokines. After this inflammatory burst, these cells undergo apoptotic cell death. We have recently demonstrated that both virus-induced immune mediator production and apoptosis were induced through Toll-like receptor 2 (TLR2) signaling. Based upon these findings, we hypothesized that the inhibition of TLR2 signaling may serve as a means to alleviate excessive neuroinflammation. In the present study, we cloned four vaccinia virus (VV) proteins, which have been reported to disrupt either TLR signaling or NF-κB activation, and overexpressed them in HEK293T cells stably expressing murine TLR2 and in primary murine microglia. Using an NF-κB-driven luciferase reporter gene assay, we show that upon stimulation with HSV and Listeria monocytogenes, all four vaccinia proteins inhibited TLR2 signaling with different levels of inhibition in the TLR2-expressing cell line and primary microglia. We found similar results when microglial cells were stimulated with the TLR4 ligand LPS and the TLR9 ligand CpG ODN. Taken together, these data provide evidence that these VV proteins can function as inhibitors of TLR signaling in primary microglial cells.

Original languageEnglish (US)
Pages (from-to)5-11
Number of pages7
JournalJournal of Neuroimmune Pharmacology
Volume3
Issue number1
DOIs
StatePublished - Mar 2008

Bibliographical note

Funding Information:
Acknowledgements This work was supported by the United States Public Health Service Award MH066703. The authors thank Dr. Andrew Bowie (Trinity College, Ireland) for the A46R and A52R antibodies, Dr. Geoffrey Smith (Imperial College London, UK) for the N1L antibody, and Dr. Joanna Shisler (University of Illinois, Urbana) for the K1L antibody.

Keywords

  • HSV
  • Microglia
  • NF-κB
  • Toll-like receptors
  • Vaccinia virus

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