Elevations in the Levels of NF-κB and Inflammatory Chemotactic Factors in the Brains with Alzheimer's Disease - One Mechanism May Involve α3 Nicotinic Acetylcholine Receptor

The purpose of this study was to investigate the alterations in the levels of nuclear factor kappa Bp65 (NF-kappa Bp65), monocyte chemoattractant protein 1 (MCP-1/CCL-2) and macrophage inflammatory protein 1 alpha (MIP-1 alpha/CCL-3) in relationship to the expression of alpha 3 nicotinic acetylcholine receptor (nAChR) during the pathogenesis of Alzheimer's disease (AD). The post-mortem human brains of AD and age-matched control individuals, SH-SY5Y and U87MG cell lines exposed to beta-amyloid peptide (A beta), as well as the SH-SY5Y cells in which alpha 3 nAChR was down-regulated by siRNA were used to study the possible expression changes of the targets such as NF-kappa Bp65, MCP-1, MIP-1 alpha and alpha 3 nAChR. The immunohistochemistry results showed the increased immunoreactivities of NF-kappa Bp65, MCP-1 and MIP-1 alpha in neurons in hippocampal and temporal and frontal regions of AD brains. Levels of NF-kappa Bp65, MCP-1 and MIP-1 alpha at both protein and mRNA levels were all significantly up-regulated in SH-SY5Y and U87MG cells exposed to A beta 1-42, while expression of alpha 3 nAChRs in A beta 1-42 exposed SH-SY5Y cells was attenuated. Interestingly, in the SH-SY5Y cells subjected to alpha 3 nAChR mRNA silencing, expression of NF-kappa Bp65, MCP-1 and MIP-1 alpha was elevated. The elevated expressions of NF-kappa B and chemokines may be involved by decreased expression of alpha 3 nAChRs during the pathogenesis of AD.