Linked Life Data

19542367

Source:http://linkedlifedata.com/resource/pubmed/id/19542367

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-7-7
pubmed:abstractText
The present study investigated the influence of PGE(2), E prostanoid (EP) receptors, and their signaling pathways on matrix metalloproteinase (MMP)-1 and IL-6 expression in synovial fibroblasts (SFs) from rheumatoid arthritis (RA) patients. RASFs expressed all four EP receptors, with selective induction of EP2 by TNF-alpha. TNF-alpha time-dependently increased intracellular cAMP/protein kinase A signaling (maximum, 6-12 h) and PGE(2) secretion (maximum, 24 h). PGE(2) and the EP2 agonists butaprost or ONO-AE1-259 ((16)-9-deoxy-9beta-chloro-15-deoxy-16-hydroxy-17,17-trimethylene-19,20-didehydro PGE(1)), in turn, induced a rapid, time-dependent (maximum, 15-30 min) increase of cAMP. Additionally, cyclooxygenase-2 inhibition by NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide) reduced the TNF-alpha-induced increase in IL-6 mRNA/protein, which was restored by stimulation with PGE(2) or EP2, EP3, and EP4 agonists. In contrast, TNF-alpha-induced MMP-1 secretion was not influenced by NS-398 and diminished by PGE(2) via EP2. Finally, 3-isobutyl-1-methylxanthine enhanced the effects of PGE(2) on MMP-1, but not on IL-6 mRNA. In conclusion, PGE(2) differentially affects TNF-alpha-induced mRNA expression of proinflammatory IL-6 and prodestructive MMP-1 regarding the usage of EP receptors and the dependency on cAMP. Although specific blockade of EP2 receptors is considered a promising therapeutic strategy in RA, opposite regulation of proinflammatory IL-6 and prodestructive MMP-1 by PGE(2) via EP2 may require more complex approaches to successfully inhibit the cyclooxygenase-1/2 cAMP axis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
183
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1328-36
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Prostaglandin E2 differentially modulates proinflammatory/prodestructive effects of TNF-alpha on synovial fibroblasts via specific E prostanoid receptors/cAMP.
pubmed:affiliation
Experimental Rheumatology Unit, Department of Orthopedics, University Hospital Jena, Jena, Germany. elke.kunisch@med.uni-jena.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural