title: Role of Toll-like receptor 4 in inflammatory reactions of hippocampal neurons.
abstract: Lipopolysaccharide stimulates Toll-like receptor 4 on immune cells to produce immune mediators. Toll-like receptor 4 is also expressed by non-immune cells, which can be stimulated by lipopolysaccharide. However, whether Toll-like receptor 4 is expressed by primary cultured hippocampal neurons and its specific role in lipopolysaccharide-induced neuroinflammation is currently undefined. In this study, Toll-like receptor 4 antibody blocking was used to analyze the Toll-like receptor 4 signaling pathway and changes in inflammation of lipopolysaccharide stimulated hippocampal neurons. Immunofluorescence showed that Toll-like receptor 4 protein was mainly located in the membrane of hippocampal neurons. Quantitative reverse transcription-PCR and western blot assay showed that after stimulation of lipopolysaccharide, the mRNA and protein levels of Toll-like receptor 4 and the mRNA levels of interleukin-1β and tumor necrosis factor-α were significantly increased. In addition, there was increased phosphorylation and degradation of kappa B α inhibitor in the cytosol and increased nuclear factor-κB p65 expression in the nuclei. Pretreatment with Toll-like receptor 4 antibody could almost completely block this increase. These experimental findings indicate that lipopolysaccharide participates in neuroinflammation by stimulating Toll-like receptor 4/nuclear factor-κB pathway in hippocampal neurons, which may be both "passive victims" and "activators" of neuroinflammation.
authors.affiliation: Department of Pathophysiology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Yae
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pathophysiology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Pediatrics, the First People's Hospital of Nantong, Nantong 226001, Jiangsu Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Zhou
keywords: Toll-like receptor 4; grants-supported paper; hippocampus; inflammation; interleukin-1 beta; lipopolysaccharide; neural regeneration; neurons; neuroregeneration; nuclear factor-kappa B; tumor necrosis factor-alpha