Abstract
It has been shown that the accumulation of prion in the cytoplasm can result in neurodegenerative disorders. Synthetic prion peptide 106–126 (PrP) is a glycoprotein that is expressed predominantly by neurons and other cells, including glial cells. Prion-induced chronic neurodegeneration has a substantial inflammatory component, and an increase in the levels of matrix metalloproteinases (MMPs) may play an important role in neurodegenerative development and progression. However, the expression of MMPs in PrP induced rat astrocytes and microglia has not yet been compared. Thus, in this study, we examined the fluorescence intensity of CD11b positive microglia and Glial Fibrillary Acidic Protein (GFAP) positive astro-cytes and found that the fluorescent intensity was increased following incubation with PrP at 24 hours in a dose-dependent manner. We also observed an increase in interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) protein expression, which are initial inflammatory cytokines, in both PrP induced astrocytes and microglia. Furthermore, an increase MMP-1, 3 and 11 expressions in PrP induced astro-cytes and microglia was observed by real time PCR. Our results demonstrated PrP induced activation of astrocytes and microglia respectively, which resulted in an increase in inflammatory cytokines and MMPs expression. These results provide the insight into the different sensitivities of glial cells to PrP.
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Betmouni, S., Perry, V.H. and Gordon, J.L. (1996). Evidence for an early inflammatory response in the central nervous system of mice with scrapie. Neuroscience. 74, 1–5.
Choi, D.H., Kim, E.M., Son, H.J., Joh, T.H., Kim, Y.S., Kim, D., Flint Beal, M. and Hwang, O. (2008). A novel intracellular role of matrix metalloproteinase-3 during apoptosis of dopaminergic cells. J. Neurochem., 106, 405–415.
Crocker, S.J, Frausto, R.F., Whitton, J.L. and Milner, R. (2008). A novel method to establish microglia-free astrocyte cultures: Comparison of matrix metalloproteinase expression profiles in pure cultures of astrocytes and microglia. Glia., 56, 1187–1198.
Crocker, S.J., Milner, R., Pham-Mitchell, N. and Campbell, I.L. (2006). Cell and agonist-specific regulation of genes for matrix metalloproteinases and their tissue inhibitors by primary glial cells. J. Neurochem., 98, 812–823.
Crocker, S.J., Pagenstecher, A. and Campbell, I.L. (2004). The TIMPs tango with MMPs and more in the central nervous system. J. Neurosci. Res., 75, 1–11.
Forloni, G., Angeretti, N., Chiesa, R., Monzani, E., Salmona, M., Bugiani, O. and Tagliavini, F. (1993). Neurotoxicity of a prion protein fragment. Nature. 362, 543–546.
Guiroy, D.C., Wakayama, I., Liberski, P.P. and Gajdusek, D.C. (1994). Relationship of microglia and scrapie amyloid-immunoreactive plaques in kuru, Creutzfeldt-Jakob disease and Ger-stmann-Straussler syndrome. Acta. Neuropathol., 87, 526–530.
Gurney, K.J., Estrada, E.Y. and Rosenberg, G.A. (2006). Blood-brain barrier disruption by stromelysin-1 facilitates neutrophil infiltration in neuroinflammation. Neurobiol. Dis., 23, 87–96.
Haorah, J., Ramirez, S.H., Schall, K., Smith, D., Pandya, R. and Persidsky, Y. (2007). Oxidative stress activates protein tyrosine kinase and matrix metalloproteinases leading to blood-brain barrier dysfunction. J. Neurochem., 101, 566–576
Hafiz, F.B. and Brown, D.R. (2000). A model for the mechanism of astrogliosis in prion disease. Mol. Cell Neurosci., 16, 221–232.
Kim, Y.S., Kim, S.S., Cho, J.J., Choi, D.H., Hwang, O., Shin, D.H., Chun, H.S., Beal, M.F. and Joh, T.H. (2005). Matrix metalloproteinase-3: a novel signaling proteinase from apoptotic neuronal cells that activates microglia. J. Neurosci., 25, 3701–3711.
Larsen, P.H., Wells, J.E., Stallcup, W.B., Opdenakker, G. and Yong, V.W. (2003). Matrix metalloproteinase-9 facilitates remy-elination in part by processing the inhibitory NG2 proteogly-can. J. Neurosci., 23, 11127–11135.
Le, Y., Yazawa, H., Gong, W., Yu, Z., Ferrans, V.J., Murphy, P.M. and Wang, J.M. (2001). The neurotoxic prion peptide fragment PrP(106–126) is a chemotactic agonist for theGprotein-coupled receptor formyl peptide receptor-like 1. J. Immunol., 166, 1448–1451.
Meda, L., Baron, P. and Scarlato, G. (2001). Glial activation in Alzheimer’s disease: the role of Abeta and its associated proteins. Neurobiol. Aging. 22, 885–893.
Pagenstecher, A., Stalder, A.K., Kincaid, C.L., Shapiro, S.D. and Campbell, I.L. (1998). Differential expression of matrix metal-loproteinase and tissue inhibitor of matrix metalloproteinase genes in the mouse central nervous system in normal and inflammatory states. Am. J. Pathol., 152, 729–741.
Proost, P., Van Damme, J. and Opdenakker, G. (1993). Leukocyte gelatinase B cleavage releases encephalitogens form human myelin basic protein. Biochem. Biophys. Res. Comm., 192, 1175–1181.
Rezaie, P. and Lantos, P.L. (2001). Microglia and the pathogenesis of spongiform encephalopathies. Brain Res. Rev., 35, 55–72.
Shim, S., Kim, S., Choi, D.S., Kwon, Y.B. and Kwon, J. (2011). Anti-inflammatory effects of [6]-shogaol: potential roles of HDAC inhibition and HSP70 induction. Food Chem. Toxicol., 49, 2734–2740.
Williams, A., Van Dam, A.M., Ritchie, D., Eikelenboom, P. and Fraser, H. (1997). Immunocytochemical appearance of cytok-ines, prostaglandin E2 and lipocortin-1 in the CNS during the incubation period of murine scrapie correlates with progressive PrP accumulations. Brain Res., 754, 171–180.
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Song, K., Na, JY., Oh, MH. et al. Synthetic Prion Peptide 106–126 Resulted in an Increase Matrix Metalloproteinases and Inflammatory Cytokines from Rat Astrocytes and Microglial Cells. Toxicol Res. 28, 5–9 (2012). https://doi.org/10.5487/TR.2012.28.1.005
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DOI: https://doi.org/10.5487/TR.2012.28.1.005