title: The role of TLR2/JNK/NF-κB pathway in amyloid β peptide-induced inflammatory response in mouse NG108-15 neural cells.
abstract: The TLR2-mediated neuroinflammatory activation has been involved in the pathogenesis of Alzheimer's disease (AD) associated with amyloid β(Aβ) deposition. In neuronal damage, JNK and NF-κB pathways contribute to TLR2-dependent secretion of proinflammatory cytokines. However, the role of TLR2/JNK/NF-κB pathway on Aβ-induced inflammatory response in nerve cell damage remains unclear. In the present study, Aβ1-42 was used to induce mouse NG108-15 neural cell injury. The cell viability was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT). The levels of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein(MCP)-1 and interleukin (IL)-10 in culture supernatant were measured by ELISA. western blot analysis was performed to detect the expressions of JNK and p-65 NF-κB proteins. Immunofluorescence assay was also performed to examine the p-JNK and p-65 NF-κB activation. As a result, Aβ1-42 incubation for 36 h inhibited remarkedly the cell viability of NG108-15, and increased significantly the levels of inflammatory cytokines TNF-α, MCP-1 and IL-10, as well as enhanced the expressions of JNK and p-65 NF-κB in western blot analysis and immunofluorescence assay. However, the pre-incubation with anti-TLR2 (OPN301, 1 μg/ml) or JNK inhibitor SP600125 (10 μg/ml) prior to Aβ1-42 administration, these upregulation events were all reduced. These results suggested that the induction of Aβ1-42 on proinflammatory cytokine generation might be associated with TLR2-dependent JNK/NF-κB signal pathway, at least partially. Our findings indicated that blockade of TLR2/JNK/NF-κB pathway could be beneficial in the pathogenesis of AD.
authors.affiliation: Department of Neurology, Jintan People's Hospital, Jiangsu, Jintan 213200, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.forename: Jianqin
authors.initials: J
authors.lastname: Xue
authors.forename: Wenhui
authors.initials: W
authors.lastname: Leng
mesh_terms: D016229:Amyloid beta-Peptides; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D016328:NF-kappa B; D010446:Peptide Fragments; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C075222:amyloid beta-protein (1-42); D048031:JNK Mitogen-Activated Protein Kinases
keywords: AD; Alzheimer's disease; Aβ; Aβ deposition; ECL; ELISA; IL-10; IPP; Image pro plus; JNK; MCP-1; MTT; NF-κB; Neuroinflammatory; OD; TLR2; TLR2/JNK/NF-κB; TNF-α; amyloid-beta; c-Jun N-terminal kinase; enhanced chemiluminescence; enzyme linked immunosorbent assay; interleukin-10; methylthiazolyldiphenyl-tetrazolium bromide; monocyte chemoattractant protein-1; nuclear factor-κB; optical density; toll-like receptor-2; tumor necrosis factor-α