Evidence for a detrimental role of TLR8 in ischemic stroke

Tang, Sung-Chun, Yeh, Shin-Joe, Li, Yu-I, Wang Yu-Chi, Baik, Sang-Ha, Santro, Tomislav, Widiapradja, Alexander, Manzanero, Silvia, Sobey, Christopher G., Jo, Dong-Gyu, Arumugam, Thiruma V. and Jeng, Jiann-Shing (2013) Evidence for a detrimental role of TLR8 in ischemic stroke. Experimental Neurology, 250 341-347. doi:10.1016/j.expneurol.2013.10.012


Author Tang, Sung-Chun
Yeh, Shin-Joe
Li, Yu-I
Wang Yu-Chi
Baik, Sang-Ha
Santro, Tomislav
Widiapradja, Alexander
Manzanero, Silvia
Sobey, Christopher G.
Jo, Dong-Gyu
Arumugam, Thiruma V.
Jeng, Jiann-Shing
Title Evidence for a detrimental role of TLR8 in ischemic stroke
Journal name Experimental Neurology   Check publisher's open access policy
ISSN 0014-4886
1090-2430
Publication date 2013-01-01
Sub-type Article (original research)
DOI 10.1016/j.expneurol.2013.10.012
Volume 250
Start page 341
End page 347
Total pages 7
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Collection year 2014
Language eng
Subject 2808 Neurology
2806 Developmental Neuroscience
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.
Keyword Apoptosis
Brain injury
Ischemic stroke
R848
TLR8
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
 
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Created: Fri, 29 Nov 2013, 22:10:48 EST by Anthony Yeates on behalf of School of Biomedical Sciences