Abstract
Background
Inflammation plays a central role in many neurodegenerative diseases, including Parkinson’s, Alzheimer’s, multiple sclerosis, amyotrophic lateral sclerosis, and AIDS dementia. Microglia are the resident macrophages of the central nervous system and are the cells primarily responsible for the inflammatory component of these diseases.
Methods
Using gene expression profiling, we compared the profile of the neurospecific microglial cell line BV-2 after LPS stimulation to that of a macrophage cell line (J774A.1) stimulated with LPS.
Results
A set of 77 genes that were modulated only in microglial cells after LPS stimulation was identified. One gene of interest, Gng12, was investigated further to determine its ability to modify the inflammatory response. Specifically, Gng12 mRNA levels were transiently increased after LPS stimulation. In addition, overall levels of Gng12 mRNA after LPS stimulation were significantly higher in BV-2 cells as compared to macrophage cells.
Conclusion
Modulating Gng12 mRNA levels using RNAi revealed a novel role for the factor in the negative regulation of the overall inflammatory response as based on effects on nitrite and TNFα levels. These data suggest that Gng12 is a negative regulator of the LPS response and may be an important factor in the overall inflammatory signaling cascade.
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Acknowledgments
We would like to thank Paratek Pharmaceuticals for supporting this research.
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Responsible Editor: G. Wallace.
An erratum to this article can be found at http://dx.doi.org/10.1007/s00011-009-0075-x
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11_2009_62_MOESM1_ESM.doc
Genes upregulated in BV-2 cells but not upregulated in J774 cells. BV-2 cells were exposed to 100 ng/mL LPS for 4 h, after which total RNA was collected and hybridized to Affymetrix MOE430A chips. Only genes up-regulated more than twofold in both experiments were considered significant. Genes up-regulated in BV-2 cells were compared to a list of genes up-regulated by LPS in J774 cells provided by Paratek Pharmaceuticals. Fold change shown is the mean of two experiments (DOC 117 kb)
11_2009_62_MOESM2_ESM.xls
All genes up- and down-regulated by LPS in BV-2 cells. BV-2 cells were exposed to 100 ng/mL LPS for 4 h, after which total RNA was collected and hybridized to Affymetrix MOE430A chips. Only genes up- or down-regulated more than twofold in both experiments were considered significant. Fold change shown is the mean of two experiments (XLS 127 kb)
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Larson, K.C., Draper, M.P., Lipko, M. et al. Gng12 is a novel negative regulator of LPS-induced inflammation in the microglial cell line BV-2. Inflamm. Res. 59, 15–22 (2010). https://doi.org/10.1007/s00011-009-0062-2
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DOI: https://doi.org/10.1007/s00011-009-0062-2