The role of TLR2/JNK/NF-κB pathway in amyloid β peptide-induced inflammatory response in mouse NG108-15 neural cells.

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.