Microglial Toll-like Receptor 2 Contributes to Kainic Acid-induced Glial Activation and Hippocampal Neuronal Cell Death

Authors
Hong, JinpyoCho, Ik-HyunKwak, Kyung IlSuh, Eun ChengSeo, JinsooMin, Hyun JungChoi, Se-YoungKim, Chong-HyunPark, Seung HwaJo, Eun-KyeongLee, SoojinLee, Kyung EunLee, Sung Joong
Issue Date
2010-12
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.285, no.50, pp.39447 - 39457
Abstract
Recent studies indicate that Toll-like receptors (TLRs), originally identified as infectious agent receptors, also mediate sterile inflammatory responses during tissue damage. In this study, we investigated the role of TLR2 in excitotoxic hippocampal cell death using TLR2 knock-out (KO) mice. TLR2 expression was up-regulated in microglia in the ipsilateral hippocampus of kainic acid (KA)-injected mice. KA-mediated hippocampal cell death was significantly reduced in TLR2 KO mice compared with wild-type (WT) mice. Similarly, KA-induced glial activation and proinflammatory gene expression in the hippocampus were compromised in TLR2 KO mice. In addition, neurons in organotypic hippocampal slice cultures (OHSCs) from TLR2 KO mouse brains were less susceptible to KA excitotoxicity than WT OHSCs. This protection is partly attributed to decreased expression of proinflammatory genes, such as TNF-alpha and IL-1 beta in TLR2 KO mice OHSCs. These data demonstrate conclusively that TLR2 signaling in microglia contributes to KA-mediated innate immune responses and hippocampal excitotoxicity.
Keywords
CENTRAL-NERVOUS-SYSTEM; BRAIN-INJURY; RAT HIPPOCAMPUS; WALLERIAN DEGENERATION; STATUS EPILEPTICUS; CEREBRAL-ISCHEMIA; ENDOGENOUS LIGAND; EXPRESSION; SEIZURES; DISEASE; CENTRAL-NERVOUS-SYSTEM; BRAIN-INJURY; RAT HIPPOCAMPUS; WALLERIAN DEGENERATION; STATUS EPILEPTICUS; CEREBRAL-ISCHEMIA; ENDOGENOUS LIGAND; EXPRESSION; SEIZURES; DISEASE; TLR2; Kainic acid; Hippocampus; Cell death; epilepsy
ISSN
0021-9258
URI
https://pubs.kist.re.kr/handle/201004/130862
DOI
10.1074/jbc.M110.132522
Appears in Collections:
KIST Article > 2010
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