TY - JOUR
T1 - Evidence for a detrimental role of TLR8 in ischemic stroke
AU - Tang, Sung-Chun
AU - Yeh, Shin-Joe
AU - Li, Yu-l
AU - Wang, Yu-Chi Wang
AU - Baik, Sang-Ha
AU - Santro, Tomislav
AU - Widiapradja, Alexander
AU - Manzanero, Silvia
AU - Sobey, Christopher Graeme
AU - Jo, Dong-Gyu
AU - Arumugam, Thiruma
AU - Jeng, Jiann-Shing
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.sciencedirect.com/science/article/pii/S0014488613003154
U2 - 10.1016/j.expneurol.2013.10.012
DO - 10.1016/j.expneurol.2013.10.012
M3 - Article
VL - 250
SP - 341
EP - 347
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
ER -