|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0012472,
umls-concept:C0017262,
umls-concept:C0030685,
umls-concept:C0077274,
umls-concept:C0079904,
umls-concept:C0185117,
umls-concept:C0206116,
umls-concept:C0391871,
umls-concept:C0441655,
umls-concept:C0680255,
umls-concept:C1150587,
umls-concept:C1283071,
umls-concept:C1367731,
umls-concept:C1565860,
umls-concept:C1705323,
umls-concept:C1705632,
umls-concept:C1963578,
umls-concept:C2911684
|
|
pubmed:issue |
3
|
|
pubmed:dateCreated |
2008-11-7
|
|
pubmed:abstractText |
Activated microglia participate in neuroinflammation which contributes to neuronal damage in neurodegenerative diseases. Inhibition of microglial activation may have potential anti-inflammatory effects. Our laboratory has previously reported that triptolide, a natural biologically active compound extracted from Tripterygium wilfordii, could protect dopaminergic neurons from inflammation-mediated damage. However, the mechanism by which triptolide inhibits inflammation remains unknown. We reported here that inhibition of prostaglandin E(2) (PGE(2)) production could be a potential mechanism of triptolide to suppress inflammation. Triptolide suppressed c-jun NH2-terminal kinase (JNK) phosphorylation, cyclooxygenase 2 (COX-2) expression and PGE(2) production in microglial cultures treated with lipopolysaccharide (LPS). Triptolide also greatly inhibited the transcriptional activity, but not the DNA-binding activity of nuclear factor-kappaB (NF-kappaB) in microglia following LPS stimulation. These results indicate that triptolide might suppress NF-kappaB activity to down-regulate COX-2 expression. The LPS-stimulated transcriptional activity of NF-kappaB was suppressed by inhibition of p38MAPK, but not by that of JNK and extracellular signal-regulated kinase. Furthermore, the LPS-induced PGE(2) production was reduced by inhibiting these kinases. Taken together, these results suggest that triptolide may suppress neuroinflammation via a mechanism that involves inactivation of two parallel signaling pathways: p38-NF-kappaB-COX-2-PGE(2) and JNK-PGE(2).
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Nov
|
|
pubmed:issn |
1471-4159
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
107
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
779-88
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:18761708-Animals,
pubmed-meshheading:18761708-Blotting, Western,
pubmed-meshheading:18761708-Cells, Cultured,
pubmed-meshheading:18761708-Cyclooxygenase 2,
pubmed-meshheading:18761708-Dinoprostone,
pubmed-meshheading:18761708-Diterpenes,
pubmed-meshheading:18761708-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:18761708-Epoxy Compounds,
pubmed-meshheading:18761708-Immunosuppressive Agents,
pubmed-meshheading:18761708-Inflammation,
pubmed-meshheading:18761708-Lipopolysaccharides,
pubmed-meshheading:18761708-MAP Kinase Kinase 4,
pubmed-meshheading:18761708-Microglia,
pubmed-meshheading:18761708-NF-kappa B,
pubmed-meshheading:18761708-Phenanthrenes,
pubmed-meshheading:18761708-Rats,
pubmed-meshheading:18761708-Rats, Sprague-Dawley,
pubmed-meshheading:18761708-Signal Transduction,
pubmed-meshheading:18761708-Transfection
|
|
pubmed:year |
2008
|
|
pubmed:articleTitle |
Triptolide inhibits COX-2 expression and PGE2 release by suppressing the activity of NF-kappaB and JNK in LPS-treated microglia.
|
|
pubmed:affiliation |
Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Ministry of Education, Key Laboratory for Neuroscience, Beijing, China.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
