title: In vitro effect of prion peptide PrP 106-126 on mouse macrophages: Possible role of macrophages in transport and proliferation for prion protein.
abstract: While there is a growing consensus on the understanding that the immune system plays an important role in facilitating the spread of prion infections from the periphery to the central nervous system, little is known about the key players in the first steps of the infection and about the sites of the disease development. Owing to their subepithelial location and their migratory capacity, macrophages could be early targets for prion transportation or propagation during the later stages of disease. In order to investigate the role of macrophages, we studied in vitro the effect of exposing primary peritoneal macrophages to a synthetic peptide homologous to residues 106-126 of the human prion protein (PrP), PrP 106-126. As shown by MTT assay, macrophage viability treated with less than 50 microM PrP 106-126 for 72 h was not inhibited but slightly stimulated at 10 and 25 microM, while there was significant decrease when exposed to 100 microM PrP 106-126 for 72 h. The expressions of PrP at mRNA and protein level were up-regulated following treatment with PrP 106-126 for 72 h. Cytokine TNF-alpha production were elevated by the PrP peptide in a time-dependent manner, which demonstrated a proinflammatory response linked to the presence and progression of prion disease took place in macrophages. These findings suggested that macrophages may play roles in the transportation and replication of the infectious agent.
authors: Animal Transmissible Spongiform Encephalopathies Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, PR China.
authors: X M
authors: XM
authors: Zhou
authors: G X
authors: GX
authors: Xu
authors: D M
authors: DM
authors: Zhao
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D051379:Mice; D010455:Peptides / Q000633:toxicity*; D011328:Prions / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D010455:Peptides; D011328:Prions; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C022616:thiazolyl blue