Microglial toll-like receptor 2 contributes to kainic acid-induced glial activation and hippocampal neuronal cell death

Jinpyo Hong, Ik Hyun Cho, Kyung Il Kwak, Eun Cheng Suh, Jinsoo Seo, Hyun Jung Min, Se Young Choi, Chong Hyun Kim, Seung Hwa Park, Eun Kyeong Jo, Soojin Lee, Kyung Eun Lee, Sung Joong Lee

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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-α and IL-1β in TLR2 KO mice OHSCs. These data demonstrate conclusively that TLR2 signaling in microglia contributes to KA-mediated innate immune responses and hippocampal excitotoxicity.

Original languageEnglish
Pages (from-to)39447-39457
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number50
DOIs
StatePublished - 10 Dec 2010

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