Galanin down-regulates microglial tumor necrosis factor-alpha production by a post-transcriptional mechanism.
The neuropeptide galanin (GAL) is up-regulated following neuronal axotomy or inflammation. Since other neuropeptides act as immunomodulatory agents, we sought to determine whether GAL might affect the murine microglial cell line BV2, which expresses the GAL2 receptor. Even at very low concentrations, GAL inhibited tumor necrosis factor-alpha (TNF alpha) release but not TNF alpha mRNA levels in LPS-stimulated BV2 cells. Northern blot analysis showed that GAL inhibited the addition of a poly(A) tail, and stability assays showed that it also destabilized TNF alpha mRNA. Thus, GAL inhibits TNF alpha production by a post-transcriptional mechanism that both prevents the efficient addition of the poly(A) tail and accelerates TNF alpha mRNA degradation.
Su
Yaming
Y
Department of Biological Sciences, Rutgers University and New Jersey Institute of Technology, Newark, NJ 07102, USA.
Ganea
Doina
D
Peng
Xiaorong
X
Jonakait
G Miller
GM
D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D004660:Encephalitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019004:Galanin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; D014409:Tumor Necrosis Factor-alpha; D019004:Galanin