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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-12-12
pubmed:abstractText
The expression of cyclooxygenase-2 (COX-2) and the synthesis of prostaglandin E2 (PGE2) as well as of cytokines such as interleukin-6 (IL-6) have all been suggested to propagate neuropathology in different brain disorders such as HIV-dementia, prion diseases, stroke and Alzheimer's disease. In this report, we show that PGE2-stimulated IL-6 release in U373 MG human astroglioma cells and primary rat astrocytes. PGE2-induced intracellular cAMP formation was mediated via prostaglandin E receptor 2 (EP2), but inhibition of cAMP formation and protein kinase A or blockade of EP1/EP2 receptors did not affect PGE2-induced IL-6 synthesis. This indicates that the cAMP pathway is not part of PGE2-induced signal transduction cascade leading to IL-6 release. The EP3/EP1-receptor agonist sulprostone failed to induce IL-6 release, suggesting an involvement of EP4-like receptors. PGE2-activated p38 mitogen-activated kinase (p38 MAPK) and protein kinase C (PKC). PGE2-induced IL-6 synthesis was inhibited by specific inhibitors of p38 MAPK (SB202190) and PKC (GF203190X). Although, up to now, EP receptors have only rarely been linked to p38 MAPK or PKC activation, these results suggest that PGE2 induces IL-6 via an EP4-like receptor by the activation of PKC and p38 MAPK via an EP4-like receptor independently of cAMP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
950-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11739606-Animals, pubmed-meshheading:11739606-Astrocytes, pubmed-meshheading:11739606-Astrocytoma, pubmed-meshheading:11739606-Blotting, Western, pubmed-meshheading:11739606-Brain Neoplasms, pubmed-meshheading:11739606-Cyclic AMP, pubmed-meshheading:11739606-Dinoprostone, pubmed-meshheading:11739606-Humans, pubmed-meshheading:11739606-Interleukin-6, pubmed-meshheading:11739606-Mitogen-Activated Protein Kinases, pubmed-meshheading:11739606-Protein Kinase C, pubmed-meshheading:11739606-Rats, pubmed-meshheading:11739606-Receptors, Prostaglandin E, pubmed-meshheading:11739606-Receptors, Prostaglandin E, EP4 Subtype, pubmed-meshheading:11739606-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11739606-Tumor Cells, Cultured, pubmed-meshheading:11739606-p38 Mitogen-Activated Protein Kinases
pubmed:year
2001
pubmed:articleTitle
Mechanisms of prostaglandin E2-induced interleukin-6 release in astrocytes: possible involvement of EP4-like receptors, p38 mitogen-activated protein kinase and protein kinase C.
pubmed:affiliation
Department of Psychiatry, University of Freiburg Medical School, Freiburg, Germany. bernd_fiebich@psyallg.ukl.uni-freiburg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't