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 |
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Authors: | Na Gan Lifen Yang Ahmed Omran Jing Peng Liwen Wu Fang He Ciliu Zhang Qiulian Xiang Huimin Kong Yupin Ma Muhammad Usman Ashhab Xiaolu Deng Fei Yin |
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Institution: | 1. Department of Pediatrics, Xiangya Hospital of Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China 2. Department of Pediatrics and Neonatology, Suez Canal University, Ismailia, 41522, Egypt
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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. |
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