alpha-melanocyte-stimulating hormone inhibits NF-kappaB activation and IkappaBalpha degradation in human glioma cells and in experimental brain inflammation
| Autor: | T, Ichiyama, H, Zhao, A, Catania, S, Furukawa, J M, Lipton |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cell Nucleus
Chloramphenicol O-Acetyltransferase Inflammation Lipopolysaccharides Male Mice Inbred BALB C Transcription Genetic NF-kappa B Brain Glioma Transfection DNA-Binding Proteins Gene Expression Regulation Neoplastic Kinetics Mice Gene Expression Regulation NF-KappaB Inhibitor alpha alpha-MSH Tumor Cells Cultured Animals Cytokines Humans I-kappa B Proteins |
| Zdroj: | Experimental neurology. 157(2) |
| ISSN: | 0014-4886 |
| Popis: | The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) modulates production of proinflammatory cytokines in brain tissue and in peripheral inflammatory cells. Transcription of the genes for these proinflammatory cytokines is regulated by the nuclear factor kappaB (NF-kappaB). NF-kappaB is also activated by proinflammatory cytokines. Degradation of the cytoplasmic inhibitor IkappaBalpha protein results in activation of NF-kappaB. Because of increasing evidence that NF-kappaB is involved in brain injury and inflammation and neurodegenerative disease, we examined whether alpha-MSH inhibits activation of NF-kappaB and limits degradation of IkappaBalpha protein induced by lipopolysaccharide (LPS) in human glioma cells (A-172) and in mouse brain. Electrophoretic mobility shift assays of nuclear extracts from A-172 cells and whole mouse brains stimulated with LPS revealed that alpha-MSH does suppress NF-kappaB activation. Western blot analysis demonstrated that alpha-MSH preserved expression of IkappaBalpha protein in vitro (glioma cells) and in vivo (brain tissue). Chloramphenicol acetyltransferase assay indicated that alpha-MSH suppresses NF-kappaB-dependent reporter gene expression induced by LPS in A-172 cells. The findings are consistent with the possibility that the anti-inflammatory action of alpha-MSH in CNS inflammation occurs via modulation of NF-kappaB activation by peptide-induced inhibition of degradation of IkappaBalpha protein. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect