The Gene Expression Profile of LPS-stimulated Microglial Cells

  • Sohn, Sung-Hwa (BK21 Oriental Medical Science Center, KyungHee University) ;
  • Ko, Eun-Jung (BK21 Oriental Medical Science Center, KyungHee University) ;
  • Kim, Sung-Hoon (Department of Oriental Pathology, College of Oriental Medicine, KyungHee University) ;
  • Kim, Yang-Seok (BK21 Oriental Medical Science Center, KyungHee University) ;
  • Shin, Min-Kyu (BK21 Oriental Medical Science Center, KyungHee University) ;
  • Hong, Moo-Chang (BK21 Oriental Medical Science Center, KyungHee University) ;
  • Bae, Hyun-Su (BK21 Oriental Medical Science Center, KyungHee University)
  • Published : 2009.06.30

Abstract

This study was conducted to evaluate the inflammatory mechanisms of LPS-stimulated BV-2 microglial cells. The inflammation mechanism was evaluated in BV-2 cells with or without LPS treated using the Affymetrix microarray analysis system. The microarray analysis revealed that B cell receptor signaling pathway, cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, MAPK signaling pathway, Neuro-active ligand-receptor interaction, TLR signaling path-way, and T cell receptor signaling pathway-related genes were up-regulated in LPS stimulated BV-2 cells. Selected genes were validated using real time RTPCR. These results can help an effective therapeutic approach to alleviating the progression of neuro-in-flammatory diseases.

Keywords

References

  1. Ensoli, F. et al. Immune-derived cytokines in the nervous system: epigenetic instructive signals or neuropathogenic mediators? Crit Rev Immunol 19:97-116 (1999)
  2. Raines, K. W. et al. Nitric oxide inhibition of ERK1/2 activity in cells expressing neuronal nitric-oxide synthase. J Biol Chem 279:3933-3940 (2004) https://doi.org/10.1074/jbc.M304813200
  3. Hou, R. C., Chen, H. L., Tzen, J. T. & Jeng, K. C. Effect of sesame antioxidants on LPS-induced NO production by BV2 microglial cells. Neuroreport 14: 1815-1819 (2003) https://doi.org/10.1097/00001756-200310060-00011
  4. Ock, J. et al. Regulation of Toll-like receptor 4 expression and its signaling by hypoxia in cultured microglia. J Neurosci Res 85:1989-1995 (2007) https://doi.org/10.1002/jnr.21322
  5. Jung, K. K. et al. Inhibitory effect of curcumin on nitric oxide production from lipopolysaccharide-activated primary microglia. Life Sci 79:2022-2031 (2006) https://doi.org/10.1016/j.lfs.2006.06.048
  6. Akundi, R. S. et al. Signal transduction pathways regulating cyclooxygenase-2 in lipopolysaccharide-activated primary rat microglia. Glia 51:199-208 (2005) https://doi.org/10.1002/glia.20198
  7. Kim, W. K. et al. A new anti-inflammatory agent KL- 1037 represses proinflammatory cytokine and inducible nitric oxide synthase (iNOS) gene expression in activated microglia. Neuropharmacology 47:243-252 (2004) https://doi.org/10.1016/j.neuropharm.2004.03.019
  8. Nagai, A. et al. Immortalized human microglial cell line: phenotypic expression. J Neurosci Res 81:342-348 (2005) https://doi.org/10.1002/jnr.20478
  9. Rock, R. B. & Peterson, P. K. Microglia as a pharmacological target in infectious and inflammatory diseases of the brain. J Neuroimmune Pharmacol 1:117-126 (2006) https://doi.org/10.1007/s11481-006-9012-8
  10. Kim, W. K. & Ko, K. H. Potentiation of N-methyl-Daspartate-mediated neurotoxicity by immunostimulated murine microglia. J Neurosci Res 54:17-26 (1998) https://doi.org/10.1002/(SICI)1097-4547(19981001)54:1<17::AID-JNR3>3.0.CO;2-K
  11. Seo, W. G. et al. Inhibitory effect of ethyl acetate fraction from Cudrania tricuspidata on the expression of nitric oxide synthase gene in RAW 264.7 macrophages stimulated with interferon-gamma and lipopolysaccharide. Gen Pharmacol 35:21-28 (2000) https://doi.org/10.1016/S0306-3623(01)00086-6
  12. Nick, J. A. et al. Selective activation and functional significance of p38alpha mitogen-activated protein kinase in lipopolysaccharide-stimulated neutrophils. J Clin Invest 103:851-858 (1999) https://doi.org/10.1172/JCI5257
  13. Kim, C. S. et al. Effect of various implant coatings on biological responses in MG63 using cDNA microarray. J Oral Rehabil 33:368-379 (2006) https://doi.org/10.1111/j.1365-2842.2005.01553.x
  14. Wang, Y. et al. Large scale real-time PCR validation on gene expression measurements from two commercial long-oligonucleotide microarrays. BMC Genomics 7:59 (2006) https://doi.org/10.1186/1471-2164-7-59
  15. Reynolds, A. D. et al. Nitrated alpha-synuclein and microglial neuroregulatory activities. J Neuroimmune Pharmacol 3:59-74 (2008) https://doi.org/10.1007/s11481-008-9100-z
  16. Skaper, S. D. The brain as a target for inflammatory processes and neuroprotective strategies. Ann N Y Acad Sci 1122:23-34 (2007) https://doi.org/10.1196/annals.1403.002
  17. Takeda, K., Kaisho, T. & Akira, S. Toll-like receptors. Annu Rev Immunol 21:335-376 (2003) https://doi.org/10.1146/annurev.immunol.21.120601.141126
  18. Ihle, J. N. Cytokine receptor signalling. Nature 377:591-594 (1995) https://doi.org/10.1038/377591a0
  19. Leon-Ponte, M. et al. Polycationic lipids inhibit the pro-inflammatory response to LPS. Immunol Lett 96:73-83 (2005) https://doi.org/10.1016/j.imlet.2004.07.019
  20. Jiang, Y. et al. TLR4 signaling induces functional nerve growth factor receptor p75 (NTR) on mouse dendritic cells via p38MAPK and NF-kappaB pathways. Mol Immunol 45:1557-1566 (2008) https://doi.org/10.1016/j.molimm.2007.10.008
  21. Aravalli, R. N., Peterson, P. K. & Lokensgard, J. R. Toll-like receptors in defense and damage of the central nervous system. J Neuroimmune Pharmacol 2:297-312 (2007) https://doi.org/10.1007/s11481-007-9071-5
  22. Sim, S. et al. NADPH oxidase-derived reactive oxygen species-mediated activation of ERK1/2 is required for apoptosis of human neutrophils induced by Entamoeba histolytica. J Immunol 174:4279-4288 (2005) https://doi.org/10.4049/jimmunol.174.7.4279
  23. Zaragoza, C. et al. Activation of the mitogen activated protein kinase extracellular signal-regulated kinase 1 and 2 by the nitric oxide-cGMP-cGMP-dependent protein kinase axis regulates the expression of matrix metalloproteinase 13 in vascular endothelial cells. Mol Pharmacol 62:927-935 (2002) https://doi.org/10.1124/mol.62.4.927