Hong, Jinpyo Cho, Ik-Hyun Kwak, Kyung Il Suh, Eun Cheng Seo, Jinsoo Min, Hyun Jung Choi, Se-Young Kim, Chong-Hyun Park, Seung Hwa Jo, Eun-Kyeong Lee, Soojin Lee, Kyung Eun Lee, Sung Joong 2024-01-20T18:03:14Z 2024-01-20T18:03:14Z 2021-09-05 2010-12 0021-9258 https://pubs.kist.re.kr/handle/201004/130862 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. English AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC CENTRAL-NERVOUS-SYSTEM BRAIN-INJURY RAT HIPPOCAMPUS WALLERIAN DEGENERATION STATUS EPILEPTICUS CEREBRAL-ISCHEMIA ENDOGENOUS LIGAND EXPRESSION SEIZURES DISEASE Microglial Toll-like Receptor 2 Contributes to Kainic Acid-induced Glial Activation and Hippocampal Neuronal Cell Death Article 10.1074/jbc.M110.132522 1 JOURNAL OF BIOLOGICAL CHEMISTRY, v.285, no.50, pp.39447 - 39457 JOURNAL OF BIOLOGICAL CHEMISTRY 285 50 39447 39457 scie scopus 000284941300071 2-s2.0-78649808560 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article 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