Prion Peptide PrP106-126 Induces Inducible Nitric Oxide Synthase and Proinflammatory Cytokine Gene Expression Through the Activation of NF-kappa B in Macrophage Cells

摘要

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-kappa B) upon exposure to PrP106-126 and its role in PrP106-126-induced upregulation of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines (interleukin [IL]-1 beta, tumor necrosis factor [TNF]-alpha, 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-kappa B activation; that proinflammatory cytokines gene expression was elevated in macrophages upon exposure to PrP106-126; and that NF-kappa B 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-kappa B, which in turn stimulates gene expression of iNOS and proinflammatory cytokines in Ana-1 macrophages.