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p38 map kinase regulates TNF-alpha production in human astrocytes and microglia by multiple mechanisms.

Authors
Lee, YB; Schrader, JW; Kim, SU
Citation
Cytokine, 12(7):874-880, 2000
Journal Title
Cytokine
ISSN
1043-46661096-0023
Abstract
In the vertebrate central nervous system (CNS), tumour necrosis factor-alpha (TNF-alpha) is produced by astrocytes and microglia and mediates cell injury in nerve cells and oligodendrocytes. In the present study, we have used a specific inhibitor of p38 MAP kinase, SB203580 to examine the role of p38 MAP kinase in regulation of TNF-alpha production in human astrocytes and microglia in terms of levels of mRNA and secreted protein. A reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed that increased levels of TNF-alpha mRNA were induced in astrocytes by IL-1beta treatment, and in microglia by bacterial lipopolysaccharide (LPS). In microglia, treatment with SB203580 reduced the level of TNF-alpha mRNA, but in astrocytes it did not. However, the secretion of TNF-alpha by both astrocytes and microglia was markedly inhibited by SB203580 at a low concentration. TNF-alpha secretion was reduced approximately 80% in astrocytes and 85% in microglia. The results demonstrate a key role played by p38 MAP kinase in upregulation of TNF-alpha mRNA levels in LPS-activated human microglia, whereas p38 MAP kinase is involved in post-transcriptional regulation of TNF-alpha production at translational level in IL-1beta-activated human astrocytes.
MeSH terms
Astrocytes/cytology/drug effects/*metabolismCells, CulturedEnzyme Inhibitors/pharmacologyHumansImidazoles/pharmacologyInterleukin-1/pharmacologyLipopolysaccharides/pharmacologyMicroglia/cytology/drug effects/*metabolismMitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolismPyridines/pharmacologyRNA, Messenger/metabolismTumor Necrosis Factor-alpha/*biosynthesis/geneticsp38 Mitogen-Activated Protein Kinases
DOI
10.1006/cyto.2000.0688
PMID
10880231
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
Journal Papers > Research Organization > Institute for Medical Sciences
AJOU Authors
이, 용범김, 승업
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