title: Differential expression of miRNA-146a-regulated inflammatory genes in human primary neural, astroglial and microglial cells.
abstract: MicroRNA-146a (miRNA-146a) is an inducible, 22 nucleotide, small RNA over-expressed in Alzheimer's disease (AD) brain. Up-regulated miRNA-146a targets several inflammation-related and membrane-associated messenger RNAs (mRNAs), including those encoding complement factor-H (CFH) and the interleukin-1 receptor associated kinase-1 (IRAK-1), resulting in significant decreases in their expression (p<0.05, ANOVA). In this study we assayed miRNA-146a, CFH, IRAK-1 and tetraspanin-12 (TSPAN12), abundances in primary human neuronal-glial (HNG) co-cultures, in human astroglial (HAG) and microglial (HMG) cells stressed with Aβ42 peptide and tumor necrosis factor alpha (TNFα). The results indicate a consistent inverse relationship between miRNA-146a and CFH, IRAK-1 and TSPAN12 expression levels, and indicate that HNG, HAG and HMG cell types each respond differently to Aβ42-peptide+TNFα-triggered stress. While the strongest miRNA-146a-IRAK-1 response was found in HAG cells, the largest miRNA-146a-TSPAN12 response was found in HNG cells, and the most significant miRNA-146a-CFH changes were found in HMG cells, the 'resident scavenging macrophages' of the brain.
authors.affiliation: LSU Neuroscience Center, Department of Ophthalmology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
authors.forename: Yuan Yuan
authors.initials: YY
authors.lastname: Li
authors.forename: Jian Guo
authors.initials: JG
authors.lastname: Cui
authors.forename: Prerna
authors.initials: P
authors.lastname: Dua
authors.forename: Aileen I
authors.initials: AI
authors.lastname: Pogue
authors.forename: Surjyadipta
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Lukiw
mesh_terms: D016229:Amyloid beta-Peptides / Q000502:physiology; D001253:Astrocytes / Q000473:pathology / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017242:Complement Factor H / Q000037:antagonists & inhibitors / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D017628:Microglia / Q000473:pathology / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D018836:Inflammation Mediators; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D017242:Complement Factor H