title: NF-кB-regulated micro RNAs (miRNAs) in primary human brain cells.
abstract: Micro RNAs (miRNAs), small and labile ~22 nucleotide-sized fragments of single stranded RNA, are important regulators of messenger (mRNA) complexity and in shaping the transcriptome of a cell. In this communication, we utilized amyloid beta 42 (Aβ42) peptides and interleukin-1beta (IL-1β) as a combinatorial, physiologically-relevant stress to induce miRNAs in human primary neural (HNG) cells (a co-culture of neurons and astroglia). Specific miRNA up-regulation was monitored using miRNA arrays, Northern micro-dot blots and RT-PCR. Selective NF-кB translocation and DNA binding inhibitors, including the chelator and anti-oxidant pyrollidine dithiocarbamate (PDTC) and the polyphenolic resveratrol analog CAY10512 (trans-3,5,4'-trihydroxystilbene), indicated the NF-кB sensitivity of several brain miRNAs, including miRNA-9, miRNA-125b and miRNA-146a. The inducible miRNA-125b and miRNA-146a, and their verified mRNA targets, including 15-lipoxygenase (15-LOX), synapsin-2 (SYN-2), complement factor H (CFH) and tetraspanin-12 (TSPAN12), suggests complex and highly interactive roles for NF-кB, miRNA-125b and miRNA-146a. These data further indicate that just two NF-кB-mediated miRNAs have tremendous potential to contribute to the regulation of neurotrophic support, synaptogenesis, neuroinflammation, innate immune signaling and amyloidogenesis in stressed primary neural cells of the human brain.
authors.affiliation: LSU Neuroscience Center, New Orleans, LA 70112, USA. wlukiw@lsuhsc.edu
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Lukiw
mesh_terms: D000682:Amyloid / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000166:cytology* / Q000473:pathology / Q000502:physiology*; D018920:Coculture Techniques; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D035683:MicroRNAs / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics* / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology; D009457:Neuroglia / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013569:Synapses / Q000235:genetics
chemical_list: D000682:Amyloid; D035683:MicroRNAs; D016328:NF-kappa B; D009414:Nerve Growth Factors