title: Prion peptide PrP106-126 induces inducible nitric oxide synthase and proinflammatory cytokine gene expression through the activation of NF-κB in macrophage cells.
abstract: The inflammatory response in prion diseases is dominated by microglia activation. The molecular mechanisms that lie behind this inflammatory process are not very well understood. In the present study, we examined the activat2ion of nuclear factor-kappa B (NF-κB) upon exposure to PrP106-126 and its role in PrP106-126-induced upregulation of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, IL-6) in Ana-1 macrophages. The results showed that iNOS and proinflammatory cytokine release was significantly elevated in Ana-1 macrophages upon exposure to PrP106-126; that PrP106-126 treatment led to a significant NF-κB activation; that proinflammatory cytokines gene expression was elevated in macrophages upon exposure to PrP106-126; and that NF-κB inhibition significantly abrogated PrP106-126-induced upregulation of iNOS and inflammatory cytokine mRNA expression. These results suggest that treatment with neurotoxic prion peptides leads to the activation of transcription factor NF-κB, which in turn stimulates gene expression of iNOS and proinflammatory cytokines in Ana-1 macrophages.
authors.affiliation: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.forename: Ailing
authors.initials: A
authors.lastname: Liu
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Zhou
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kouadir
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Siming
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yin
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yang
authors.forename: Deming
authors.initials: D
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011328:Prions / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D010446:Peptide Fragments; D011328:Prions; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C082632:prion protein (106-126); D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II