title: 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.
abstract: The purpose of this study was to investigate the alterations in the levels of nuclear factor κBp65 (NF-κBp65), monocyte chemoattractant protein 1 (MCP-1/CCL-2) and macrophage inflammatory protein 1α (MIP-1α/CCL-3) in relationship to the expression of α3 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 β-amyloid peptide (Aβ), as well as the SH-SY5Y cells in which α3 nAChR was down-regulated by siRNA were used to study the possible expression changes of the targets such as NF-κBp65, MCP-1, MIP-1α and α3 nAChR. The immunohistochemistry results showed the increased immunoreactivities of NF-κBp65, MCP-1 and MIP-1α in neurons in hippocampal and temporal and frontal regions of AD brains. Levels of NF-κBp65, MCP-1 and MIP-1α at both protein and mRNA levels were all significantly up-regulated in SH-SY5Y and U87MG cells exposed to Aβ1-42, while expression of α3 nAChRs in Aβ1-42 exposed SH-SY5Y cells was attenuated. Interestingly, in the SH-SY5Y cells subjected to α3 nAChR mRNA silencing, expression of NF-κBp65, MCP-1 and MIP-1α was elevated. The elevated expressions of NF- κB and chemokines may be involved by decreased expression of α3 nAChRs during the pathogenesis of AD.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liao
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Qi
authors.forename: Ying
authors.initials: Y
authors.lastname: Cao
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Yu
authors.forename: Rivka
authors.initials: R
authors.lastname: Ravid
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Jin-Jing
authors.initials: JJ
authors.lastname: Pei
authors.affiliation: Department of Pathology in the Affiliated Hospital and The Key Lab of Medical Molecular Biology, Guizhou Medical University, Guiyang 550004, P.R. of China.
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Guan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009447:Neuroblastoma; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D002630:Chemotactic Factors; D005904:Glial Fibrillary Acidic Protein; D016328:NF-kappa B; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; C111835:CCL2 protein, human