rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
1-2
|
pubmed:dateCreated |
2005-6-13
|
pubmed:abstractText |
Glial activation and inflammation following brain injury may initiate and maintain the process of neurodegeneration. Both glia and neurons synthesize proinflammatory mediators such as interleukin 1 beta (IL-1beta), cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and prostaglandins. The molecular mechanisms by which IL-1beta regulates inflammatory genes such as cPLA2 and COX-2 in glial and neuronal cells are poorly understood. We have studied IL-1beta-mediated gene regulation in an established glial and neuronal human cell lines. We report that IL-1beta induced cPLA2 and COX-2 mRNA and protein expression and subsequent prostaglandin E2 (PGE2) release in a time-dependent manner in H4 neuroglioma cells. Both SB203580 and PD98059 [p38 and p42/44 mitogen-activated protein kinase (MAPKs) inhibitors, respectively] reduced IL-1beta-induced PGE2 production, while only SB203580 reduced both cPLA2 and COX-2 expression. Similarly, in SKNSH neuroblastoma cells, both SB203580 and PD98059 reduced IL-1beta-induced PGE2 release, with no detectable COX-2 and cPLA2 protein expression in these cells. Our results indicate that the signaling mechanisms of p38 and p42/44 MAPKs play a role in IL-1beta-mediated PGE2 release in both of these cell lines, with differences upstream at the level of cPLA(2)/COX-2 expression. IL-1beta-induced cPLA2 and COX-2 gene expression is modulated through the p38 MAPK pathway in both neuroglioma and neuroblastoma cells. Understanding the signaling mechanisms involved in IL-1beta-mediated inflammatory processes in both glia and neuronal cells may provide potential targets for therapeutic intervention for neurological disorders.
|
pubmed:grant |
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Group IV Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jun
|
pubmed:issn |
0169-328X
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
13
|
pubmed:volume |
137
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
202-12
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:15950779-Brain,
pubmed-meshheading:15950779-Brain Damage, Chronic,
pubmed-meshheading:15950779-Cell Line, Tumor,
pubmed-meshheading:15950779-Cyclooxygenase 2,
pubmed-meshheading:15950779-Dinoprostone,
pubmed-meshheading:15950779-Encephalitis,
pubmed-meshheading:15950779-Enzyme Inhibitors,
pubmed-meshheading:15950779-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:15950779-Glioma,
pubmed-meshheading:15950779-Group IV Phospholipases A2,
pubmed-meshheading:15950779-Humans,
pubmed-meshheading:15950779-Interleukin-1,
pubmed-meshheading:15950779-MAP Kinase Signaling System,
pubmed-meshheading:15950779-Membrane Proteins,
pubmed-meshheading:15950779-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:15950779-Nerve Degeneration,
pubmed-meshheading:15950779-Neuroblastoma,
pubmed-meshheading:15950779-Neurons,
pubmed-meshheading:15950779-Phospholipases A,
pubmed-meshheading:15950779-Phospholipases A2,
pubmed-meshheading:15950779-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:15950779-RNA, Messenger,
pubmed-meshheading:15950779-p38 Mitogen-Activated Protein Kinases
|
pubmed:year |
2005
|
pubmed:articleTitle |
Regulation of the cyclooxygenase-2 system by interleukin-1beta through mitogen-activated protein kinase signaling pathways: a comparative study of human neuroglioma and neuroblastoma cells.
|
pubmed:affiliation |
M3-104, Division of Pharmacology, 2411 Holmes, UMKC School of Medicine, University of Missouri-Kansas City, MO 64108, USA.
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|