https://scholars.lib.ntu.edu.tw/handle/123456789/590506
標題: | Evidence for a detrimental role of TLR8 in ischemic stroke | 作者: | SUNG-CHUN TANG SHIN-JOE YEH Li Y.-I. Wang Y.-C. Baik S.-H. Santro T. Widiapradja A. Manzanero S. Sobey C.G. Jo D.-G. Arumugam T.V. JIANN-SHING JENG |
公開日期: | 2013 | 卷: | 250 | 起(迄)頁: | 341-347 | 來源出版物: | Experimental Neurology | 摘要: | 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84887194808&doi=10.1016%2fj.expneurol.2013.10.012&partnerID=40&md5=1a838746aba448d46dbd965165ab75c1 https://scholars.lib.ntu.edu.tw/handle/123456789/590506 |
ISSN: | 144886 | DOI: | 10.1016/j.expneurol.2013.10.012 | SDG/關鍵字: | 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 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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