Gng12 is a novel negative regulator of LPS-induced inflammation in the microglial cell line BV-2.
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.


CONCLUSIONS
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 TNFalpha 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.
Larson
Kelley C
KC
Galenea Corporation, Cambridge, MA, USA. kelleyclarson@yahoo.com
Lipko
Maciej
M
Dabrowski
Michal
M
Draper
Michael P
MP
D000818:Animals; D002460:Cell Line; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics / Q000502:physiology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D044388:GTP-Binding Protein gamma Subunits; C548441:Gng12 protein, mouse; D008070:Lipopolysaccharides; D009573:Nitrites; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019204:GTP-Binding Proteins