title: Myoloid-related protein 8, an endogenous ligand of Toll-like receptor 4, is involved in epileptogenesis of mesial temporal lobe epilepsy via activation of the nuclear factor-κB pathway in astrocytes.
abstract: The role of Toll-like receptor 4 (TLR4) in the activation of innate immunity has been extensively studied in the past several years. Here, we are the first to report that myeloid-related protein 8 (MRP8), an endogenous TLR4 ligand, is involved in the epileptogenesis of mesial temporal lobe epilepsy (MTLE). We find that the expression of MRP8, TLR4, and interleukin 1-β (IL-1β) was upregulated in a MTLE model during both acute and chronic disease stages. We next investigated the possible roles played by astrocytes, which have been shown to be the major source of IL-1β during epilepsy. Stimulation via MRP8 led to the induction of IL-1β in astrocytes in vitro, accompanied by the activation of Nuclear Factor-κB, while knockdown of TLR4 or inhibition of NF-κB in astrocytes prevented this IL-1β induction. Thus, MRP8 may potentiate the perpetuation of MTLE by activating the NF-κB pathway in astrocytes, and could be a new target for anticonvulsant therapies.
authors: Department of Pediatrics, Xiangya Hospital of Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.
authors: Na
authors: N
authors: Gan
authors: Lifen
authors: L
authors: Yang
authors: Ahmed
authors: A
authors: Omran
authors: Jing
authors: J
authors: Peng
authors: Liwen
authors: L
authors: Wu
authors: Fang
authors: F
authors: He
authors: Ciliu
authors: C
authors: Zhang
authors: Qiulian
authors: Q
authors: Xiang
authors: Huimin
authors: H
authors: Kong
authors: Yupin
authors: Y
authors: Ma
authors: Muhammad Usman
authors: MU
authors: Ashhab
authors: Xiaolu
authors: X
authors: Deng
authors: Fei
authors: F
authors: Yin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D040501:Calgranulin A / Q000096:biosynthesis*; D002478:Cells, Cultured; D002648:Child; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*
chemical_list: D040501:Calgranulin A; D008024:Ligands; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4
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