Toxicological Research

  • 제28권1호
  • /
  • Pages.5-9
  • /
  • 2012
  • /
  • 1976-8257(pISSN)
  • /
  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
권호 표지
DOI QR코드

DOI QR Code

Synthetic Prion Peptide 106-126 Resulted in an Increase Matrix Metalloproteinases and Inflammatory Cytokines from Rat Astrocytes and Microglial Cells

  • Song, Kib-Beum (Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Na, Ji-Young (Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Oh, Myung-Hoon (Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Kim, Sok-Ho (Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Kim, Young-Ha (Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Park, Byung-Yong (Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Shin, Gi-Wook (Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Kim, Bum-Seok (Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • You, Myung-Jo (Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Kwon, Jung-Kee (Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
  • 투고 : 2012.02.08
  • 심사 : 2012.03.21
  • 발행 : 2012.03.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

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 astrocytes 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-$1{\beta}$) and tumor necrosis factor alpha (TNF-${\alpha}$) 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 astrocytes 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.

키워드

참고문헌

  1. 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. https://doi.org/10.1016/0306-4522(96)00212-6
  2. 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 https://doi.org/10.1111/j.1471-4159.2008.05399.x
  3. 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. https://doi.org/10.1002/glia.20689
  4. 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. https://doi.org/10.1111/j.1471-4159.2006.03927.x
  5. 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. https://doi.org/10.1002/jnr.10836
  6. 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. https://doi.org/10.1038/362543a0
  7. 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 Gerstmann- Straussler syndrome. Acta. Neuropathol., 87, 526-530. https://doi.org/10.1007/BF00294180
  8. Gurney, K.J., Estrada, E.Y. and Rosenberg, G.A. (2006). Bloodbrain barrier disruption by stromelysin-1 facilitates neutrophil infiltration in neuroinflammation. Neurobiol. Dis., 23, 87-96. https://doi.org/10.1016/j.nbd.2006.02.006
  9. 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 https://doi.org/10.1111/j.1471-4159.2006.04393.x
  10. Hafiz, F.B. and Brown, D.R. (2000). A model for the mechanism of astrogliosis in prion disease. Mol. Cell Neurosci., 16, 221-232. https://doi.org/10.1006/mcne.2000.0868
  11. 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. https://doi.org/10.1523/JNEUROSCI.4346-04.2005
  12. Larsen, P.H., Wells, J.E., Stallcup, W.B., Opdenakker, G. and Yong, V.W. (2003). Matrix metalloproteinase-9 facilitates remyelination in part by processing the inhibitory NG2 proteoglycan. J. Neurosci., 23, 11127-11135.
  13. 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. https://doi.org/10.4049/jimmunol.166.3.1448
  14. 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. https://doi.org/10.1016/S0197-4580(01)00307-4
  15. Pagenstecher, A., Stalder, A.K., Kincaid, C.L., Shapiro, S.D. and Campbell, I.L. (1998). Differential expression of matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase genes in the mouse central nervous system in normal and inflammatory states. Am. J. Pathol., 152, 729-741.
  16. 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. https://doi.org/10.1006/bbrc.1993.1540
  17. Rezaie, P. and Lantos, P.L. (2001). Microglia and the pathogenesis of spongiform encephalopathies. Brain Res. Rev., 35, 55-72. https://doi.org/10.1016/S0165-0173(01)00042-X
  18. 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. https://doi.org/10.1016/j.fct.2011.08.012
  19. Williams, A., Van Dam, A.M., Ritchie, D., Eikelenboom, P. and Fraser, H. (1997). Immunocytochemical appearance of cytokines, 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. https://doi.org/10.1016/S0006-8993(97)00067-X