Evidence for a detrimental role of TLR8 in ischemic stroke Academic Article uri icon

abstract

  • Toll-like receptors (TLRs) are transmembrane pattern-recognition receptors that initiate signals in response to diverse pathogen-associated molecular patterns. Several groups have recently reported a role for TLR2 and TLR4 in ischemic stroke-induced brain injury. However, relatively little is known about the role of TLR8 in ischemic stroke. Here we provide the first evidence that TLR8 activation plays a detrimental role in stroke outcome by promoting neuronal apoptosis and T cell-mediated post-stroke inflammation. TLR8 is expressed in cerebral cortical neurons, where its levels and downstream signaling via JNK are increased in response to oxygen glucose deprivation (OGD). Treatment with a TLR8 agonist activated pro-apoptotic JNK and increased neuronal cell death during OGD. Furthermore, selective knockdown of TLR8 using siRNA protected SH-SY5Y cells following OGD, and TLR8 agonist administration in vivo increased mortality, neurological deficit and T cell infiltration following stroke. Taken together, our findings indicate a detrimental role for neuronal TLR8 signaling in the triggering of post-stroke inflammation and neuronal death.

authors

  • Tang, SC
  • Yeh, SJ
  • Li, YI
  • Wang, YC
  • Baik, SH
  • Santro, T
  • Widiapradja, A
  • Manzanero, S
  • Sobey, CG
  • Jo, DG
  • Arumugam, TV
  • Jeng, JS

publication date

  • 2013