title: Recombinant mouse prion protein alone or in combination with lipopolysaccharide alters expression of innate immunity genes in the colon of mice.
abstract: The objectives of this study were to test whether recombinant mouse (mo)PrP alone or in combination with LPS or under simulated endotoxemia would affect expression of genes related to host inflammatory and antimicrobial responses. To test our hypotheses colon tissues were collected from 16 male mice (FVB/N strain) and mounted in an Ussing chamber. Application of moPrP to the mucosal side of the colon affected genes related to TLR- and NLR- signaling and antimicrobial responses. When LPS was added on the mucosal side of the colon, genes related to TLR, Nlrp3 inflammasome, and iron transport proteins were over-expressed. Addition of LPS to the serosal side of the colon up-regulated genes related to TLR- and NLR-signaling, Nlrp3 inflammasome, and a chemokine. Treatment with both moPrP and LPS to the mucosal side of the colon upregulated genes associated with TLR, downstream signal transduction (DST), inflammatory response, attraction of dendritic cells to the site of inflammation, and the JNK-apoptosis pathway. Administration of moPrP to the mucosal side and LPS to the serosal side of the colon affected genes related to TLR- and NLR-signaling, DST, apoptosis, inflammatory response, cytokines, chemokines, and antimicrobial peptides. Overall this study suggests a potential role for moPrP as an endogenous 'danger signal' associated with activation of colon genes related to innate immunity and antibacterial responses.
authors.affiliation: a Department of Agricultural, Food and Nutritional Science ; University of Alberta , Edmonton , AB , Canada ;
authors.forename: Elda
authors.initials: E
authors.lastname: Dervishi
authors.forename: Tran H
authors.initials: TH
authors.lastname: Lam
authors.forename: Suzana M
authors.initials: SM
authors.lastname: Dunn
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Zwierzchowski
authors.forename: Fozia
authors.initials: F
authors.lastname: Saleem
authors.forename: David S
authors.initials: DS
authors.lastname: Wishart
authors.forename: Burim N
authors.initials: BN
authors.lastname: Ametaj
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects* / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D000072002:Prion Proteins; D011328:Prions / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011994:Recombinant Proteins
keywords: DST, downstream signal transduction; LPS, lipopolysaccharide; NLR, NOD like receptor; PrPC, cellular form of the prion protein; TLR, toll like receptor; Ussing chamber; antimicrobial response; colon; gene expression; lipopolysaccharide; mice; moPrPC, mouse cellular prion protein; mouse cellular prion protein