Evidence for a detrimental role of TLR8 in ischemic stroke
Journal
Experimental Neurology
Journal Volume
250
Pages
341-347
Date Issued
2013
Author(s)
Li Y.-I.
Wang Y.-C.
Baik S.-H.
Santro T.
Widiapradja A.
Manzanero S.
Sobey C.G.
Jo D.-G.
Arumugam T.V.
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. ? 2013 Elsevier Inc.
SDGs
Other Subjects
glucose; oxygen; small interfering RNA; stress activated protein kinase; toll like receptor 8; animal cell; animal experiment; animal model; animal tissue; article; brain cortex; brain ischemia; brain nerve cell; cell protection; controlled study; embryo; gene silencing; inflammation; lymphocytic infiltration; male; mortality; mouse; nerve cell necrosis; neurologic disease; neuropathology; nonhuman; priority journal; protein analysis; protein expression; protein function; receptor upregulation; signal transduction; T lymphocyte; Apoptosis; Brain injury; Ischemic stroke; R848; TLR8; Animals; Apoptosis; Blotting, Western; Cell Line; Disease Models, Animal; Flow Cytometry; Humans; Immunohistochemistry; Inflammation; Male; Mice; Mice, Inbred C57BL; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Stroke; Toll-Like Receptor 8
Type
journal article