Participation of cyclooxygenase-1 in prostaglandin E2 release from synovitis tissue in primary osteoarthritis in vitro
To investigate the relative contribution of the cyclooxygenase (COX) isoenzymes COX-1 and COX-2 to prostaglandin E2 (PGE2) release from inflamed synovial tissue in N=10 patients with primary osteoarthritis (OA) in vitro and to determine possible effects of COX inhibitors on the gene expression of sy...
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| Veröffentlicht in: | Osteoarthritis and cartilage 2004-08, Vol.12 (8), p.658-666 |
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| container_title | Osteoarthritis and cartilage |
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| creator | Knorth, Holger Dorfmüller, Peter Lebert, Rainer Schmidt, Wolfgang E Wittenberg, Ralf H Heukamp, Matthias Wiese, Matthias Willburger, Roland E |
| description | To investigate the relative contribution of the cyclooxygenase (COX) isoenzymes COX-1 and COX-2 to prostaglandin E2 (PGE2) release from inflamed synovial tissue in N=10 patients with primary osteoarthritis (OA) in vitro and to determine possible effects of COX inhibitors on the gene expression of synovial COX-1 and COX-2.
The effects of a COX-unspecific nonsteroidal anti-inflammatory drug (NSAID; diclofenac), a selective COX-1 inhibitor (SC-560) and a selective COX-2 inhibitor (SC-58125) on PGE2 release from inflamed synovial tissue (0.1-10 microM, 3 and 6 h incubation time) were compared. Release of PGE2 into the incubation media was measured by means of the enzyme-linked immunosorbent assay. Expression of synovial COX-1/-2 was quantified by means of real-time reverse transcriptase polymerase chain reaction (RT-PCR).
All agents inhibited synovial PGE2 release dose-dependently. Compared to short-term incubations, the inhibitory potency of diclofenac, SC-58125 and SC-560 was increased (0.1-10 microM) and decreased (0.1-1 microM), respectively, during 6 h: At 10 microM, SC-560 and SC-58125 had obviously lost their specificity for COX-1 and COX-2, respectively, indicated by a comparable inhibitory potency of the selective COX-1 inhibitor (86.6%) and the selective COX-2 inhibitor (96.6%) within identical tissue specimens. In contrast, at 1 microM, 83% and 62.8% inhibition was seen for diclofenac and SC-58125, respectively. SC-560 showed 30.6% inhibition (P |
| doi_str_mv | 10.1016/j.joca.2004.05.002 |
| format | Article |
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The effects of a COX-unspecific nonsteroidal anti-inflammatory drug (NSAID; diclofenac), a selective COX-1 inhibitor (SC-560) and a selective COX-2 inhibitor (SC-58125) on PGE2 release from inflamed synovial tissue (0.1-10 microM, 3 and 6 h incubation time) were compared. Release of PGE2 into the incubation media was measured by means of the enzyme-linked immunosorbent assay. Expression of synovial COX-1/-2 was quantified by means of real-time reverse transcriptase polymerase chain reaction (RT-PCR).
All agents inhibited synovial PGE2 release dose-dependently. Compared to short-term incubations, the inhibitory potency of diclofenac, SC-58125 and SC-560 was increased (0.1-10 microM) and decreased (0.1-1 microM), respectively, during 6 h: At 10 microM, SC-560 and SC-58125 had obviously lost their specificity for COX-1 and COX-2, respectively, indicated by a comparable inhibitory potency of the selective COX-1 inhibitor (86.6%) and the selective COX-2 inhibitor (96.6%) within identical tissue specimens. In contrast, at 1 microM, 83% and 62.8% inhibition was seen for diclofenac and SC-58125, respectively. SC-560 showed 30.6% inhibition (P<0.05). In contrast to synovial COX-1, RT-PCR revealed a significant induction of COX-2 through PGE2.
With respect to the concentrations studied, the data suggest that in inflamed synovial tissue in OA, up to 30% of PGE2 might be generated via the COX-1 pathway. In therapy of OA, the relative contribution of COX-1 in synovial inflammation should be considered, weighing the potency of COX-unspecific NSAID against the assumed superior gastrointestinal safety profile of selective COX-2 inhibitors.</description><identifier>ISSN: 1063-4584</identifier><identifier>DOI: 10.1016/j.joca.2004.05.002</identifier><identifier>PMID: 15262246</identifier><language>eng</language><publisher>England</publisher><subject>Aged ; Culture Techniques ; Cyclooxygenase 1 ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors - pharmacology ; Dinoprostone - metabolism ; Dose-Response Relationship, Drug ; Female ; Humans ; Isoenzymes - antagonists & inhibitors ; Isoenzymes - metabolism ; Isoenzymes - physiology ; Male ; Membrane Proteins ; Middle Aged ; Osteoarthritis, Knee - enzymology ; Osteoarthritis, Knee - metabolism ; Osteoarthritis, Knee - pathology ; Prostaglandin-Endoperoxide Synthases - metabolism ; Prostaglandin-Endoperoxide Synthases - physiology ; Severity of Illness Index ; Synovial Membrane - drug effects ; Synovial Membrane - enzymology ; Synovitis - enzymology ; Synovitis - metabolism ; Synovitis - pathology</subject><ispartof>Osteoarthritis and cartilage, 2004-08, Vol.12 (8), p.658-666</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2582-e80ff59618f492c71b4a9e2eb47cd53aa80c1e0f3972e902a82442e4a60aef313</citedby><cites>FETCH-LOGICAL-c2582-e80ff59618f492c71b4a9e2eb47cd53aa80c1e0f3972e902a82442e4a60aef313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15262246$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Knorth, Holger</creatorcontrib><creatorcontrib>Dorfmüller, Peter</creatorcontrib><creatorcontrib>Lebert, Rainer</creatorcontrib><creatorcontrib>Schmidt, Wolfgang E</creatorcontrib><creatorcontrib>Wittenberg, Ralf H</creatorcontrib><creatorcontrib>Heukamp, Matthias</creatorcontrib><creatorcontrib>Wiese, Matthias</creatorcontrib><creatorcontrib>Willburger, Roland E</creatorcontrib><title>Participation of cyclooxygenase-1 in prostaglandin E2 release from synovitis tissue in primary osteoarthritis in vitro</title><title>Osteoarthritis and cartilage</title><addtitle>Osteoarthritis Cartilage</addtitle><description>To investigate the relative contribution of the cyclooxygenase (COX) isoenzymes COX-1 and COX-2 to prostaglandin E2 (PGE2) release from inflamed synovial tissue in N=10 patients with primary osteoarthritis (OA) in vitro and to determine possible effects of COX inhibitors on the gene expression of synovial COX-1 and COX-2.
The effects of a COX-unspecific nonsteroidal anti-inflammatory drug (NSAID; diclofenac), a selective COX-1 inhibitor (SC-560) and a selective COX-2 inhibitor (SC-58125) on PGE2 release from inflamed synovial tissue (0.1-10 microM, 3 and 6 h incubation time) were compared. Release of PGE2 into the incubation media was measured by means of the enzyme-linked immunosorbent assay. Expression of synovial COX-1/-2 was quantified by means of real-time reverse transcriptase polymerase chain reaction (RT-PCR).
All agents inhibited synovial PGE2 release dose-dependently. Compared to short-term incubations, the inhibitory potency of diclofenac, SC-58125 and SC-560 was increased (0.1-10 microM) and decreased (0.1-1 microM), respectively, during 6 h: At 10 microM, SC-560 and SC-58125 had obviously lost their specificity for COX-1 and COX-2, respectively, indicated by a comparable inhibitory potency of the selective COX-1 inhibitor (86.6%) and the selective COX-2 inhibitor (96.6%) within identical tissue specimens. In contrast, at 1 microM, 83% and 62.8% inhibition was seen for diclofenac and SC-58125, respectively. SC-560 showed 30.6% inhibition (P<0.05). In contrast to synovial COX-1, RT-PCR revealed a significant induction of COX-2 through PGE2.
With respect to the concentrations studied, the data suggest that in inflamed synovial tissue in OA, up to 30% of PGE2 might be generated via the COX-1 pathway. In therapy of OA, the relative contribution of COX-1 in synovial inflammation should be considered, weighing the potency of COX-unspecific NSAID against the assumed superior gastrointestinal safety profile of selective COX-2 inhibitors.</description><subject>Aged</subject><subject>Culture Techniques</subject><subject>Cyclooxygenase 1</subject><subject>Cyclooxygenase 2</subject><subject>Cyclooxygenase 2 Inhibitors</subject><subject>Cyclooxygenase Inhibitors - pharmacology</subject><subject>Dinoprostone - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Humans</subject><subject>Isoenzymes - antagonists & inhibitors</subject><subject>Isoenzymes - metabolism</subject><subject>Isoenzymes - physiology</subject><subject>Male</subject><subject>Membrane Proteins</subject><subject>Middle Aged</subject><subject>Osteoarthritis, Knee - enzymology</subject><subject>Osteoarthritis, Knee - metabolism</subject><subject>Osteoarthritis, Knee - pathology</subject><subject>Prostaglandin-Endoperoxide Synthases - metabolism</subject><subject>Prostaglandin-Endoperoxide Synthases - physiology</subject><subject>Severity of Illness Index</subject><subject>Synovial Membrane - drug effects</subject><subject>Synovial Membrane - enzymology</subject><subject>Synovitis - enzymology</subject><subject>Synovitis - metabolism</subject><subject>Synovitis - pathology</subject><issn>1063-4584</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1PwzAMhnMAsTH4AxxQTtxaHDf9OqJpfEhIcIBzlGXOaNU2o2kn9u_JWCUOlmX5fW29D2M3AmIBIruv49oZHSOAjCGNAfCMzQVkSSTTQs7Ypfc1ACRCwAWbiRQzRJnN2f5d90Nlqp0eKtdxZ7k5mMa5n8OWOu0pErzq-K53ftDbRnebMK2Q99RQ2HLbu5b7Q-f21VB5HsqPdHJUre4PPPjIhRdf_Z8gbIKyd1fs3OrG0_XUF-zzcfWxfI5e355elg-vkcG0wIgKsDYtM1FYWaLJxVrqkpDWMjebNNG6ACMIbFLmSCWgLlBKJKkz0GQTkSzY3eluSPA9kh9UW3lDTUhCbvQqy3LEJIUgxJPQhKi-J6umBEqAOhJWtToSVkfCClIVCAfT7XR9XLe0-bdMeJNfj498xw</recordid><startdate>200408</startdate><enddate>200408</enddate><creator>Knorth, Holger</creator><creator>Dorfmüller, Peter</creator><creator>Lebert, Rainer</creator><creator>Schmidt, Wolfgang E</creator><creator>Wittenberg, Ralf H</creator><creator>Heukamp, Matthias</creator><creator>Wiese, Matthias</creator><creator>Willburger, Roland E</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200408</creationdate><title>Participation of cyclooxygenase-1 in prostaglandin E2 release from synovitis tissue in primary osteoarthritis in vitro</title><author>Knorth, Holger ; Dorfmüller, Peter ; Lebert, Rainer ; Schmidt, Wolfgang E ; Wittenberg, Ralf H ; Heukamp, Matthias ; Wiese, Matthias ; Willburger, Roland E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2582-e80ff59618f492c71b4a9e2eb47cd53aa80c1e0f3972e902a82442e4a60aef313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Aged</topic><topic>Culture Techniques</topic><topic>Cyclooxygenase 1</topic><topic>Cyclooxygenase 2</topic><topic>Cyclooxygenase 2 Inhibitors</topic><topic>Cyclooxygenase Inhibitors - pharmacology</topic><topic>Dinoprostone - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Humans</topic><topic>Isoenzymes - antagonists & inhibitors</topic><topic>Isoenzymes - metabolism</topic><topic>Isoenzymes - physiology</topic><topic>Male</topic><topic>Membrane Proteins</topic><topic>Middle Aged</topic><topic>Osteoarthritis, Knee - enzymology</topic><topic>Osteoarthritis, Knee - metabolism</topic><topic>Osteoarthritis, Knee - pathology</topic><topic>Prostaglandin-Endoperoxide Synthases - metabolism</topic><topic>Prostaglandin-Endoperoxide Synthases - physiology</topic><topic>Severity of Illness Index</topic><topic>Synovial Membrane - drug effects</topic><topic>Synovial Membrane - enzymology</topic><topic>Synovitis - enzymology</topic><topic>Synovitis - metabolism</topic><topic>Synovitis - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Knorth, Holger</creatorcontrib><creatorcontrib>Dorfmüller, Peter</creatorcontrib><creatorcontrib>Lebert, Rainer</creatorcontrib><creatorcontrib>Schmidt, Wolfgang E</creatorcontrib><creatorcontrib>Wittenberg, Ralf H</creatorcontrib><creatorcontrib>Heukamp, Matthias</creatorcontrib><creatorcontrib>Wiese, Matthias</creatorcontrib><creatorcontrib>Willburger, Roland E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Osteoarthritis and cartilage</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Knorth, Holger</au><au>Dorfmüller, Peter</au><au>Lebert, Rainer</au><au>Schmidt, Wolfgang E</au><au>Wittenberg, Ralf H</au><au>Heukamp, Matthias</au><au>Wiese, Matthias</au><au>Willburger, Roland E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Participation of cyclooxygenase-1 in prostaglandin E2 release from synovitis tissue in primary osteoarthritis in vitro</atitle><jtitle>Osteoarthritis and cartilage</jtitle><addtitle>Osteoarthritis Cartilage</addtitle><date>2004-08</date><risdate>2004</risdate><volume>12</volume><issue>8</issue><spage>658</spage><epage>666</epage><pages>658-666</pages><issn>1063-4584</issn><abstract>To investigate the relative contribution of the cyclooxygenase (COX) isoenzymes COX-1 and COX-2 to prostaglandin E2 (PGE2) release from inflamed synovial tissue in N=10 patients with primary osteoarthritis (OA) in vitro and to determine possible effects of COX inhibitors on the gene expression of synovial COX-1 and COX-2.
The effects of a COX-unspecific nonsteroidal anti-inflammatory drug (NSAID; diclofenac), a selective COX-1 inhibitor (SC-560) and a selective COX-2 inhibitor (SC-58125) on PGE2 release from inflamed synovial tissue (0.1-10 microM, 3 and 6 h incubation time) were compared. Release of PGE2 into the incubation media was measured by means of the enzyme-linked immunosorbent assay. Expression of synovial COX-1/-2 was quantified by means of real-time reverse transcriptase polymerase chain reaction (RT-PCR).
All agents inhibited synovial PGE2 release dose-dependently. Compared to short-term incubations, the inhibitory potency of diclofenac, SC-58125 and SC-560 was increased (0.1-10 microM) and decreased (0.1-1 microM), respectively, during 6 h: At 10 microM, SC-560 and SC-58125 had obviously lost their specificity for COX-1 and COX-2, respectively, indicated by a comparable inhibitory potency of the selective COX-1 inhibitor (86.6%) and the selective COX-2 inhibitor (96.6%) within identical tissue specimens. In contrast, at 1 microM, 83% and 62.8% inhibition was seen for diclofenac and SC-58125, respectively. SC-560 showed 30.6% inhibition (P<0.05). In contrast to synovial COX-1, RT-PCR revealed a significant induction of COX-2 through PGE2.
With respect to the concentrations studied, the data suggest that in inflamed synovial tissue in OA, up to 30% of PGE2 might be generated via the COX-1 pathway. In therapy of OA, the relative contribution of COX-1 in synovial inflammation should be considered, weighing the potency of COX-unspecific NSAID against the assumed superior gastrointestinal safety profile of selective COX-2 inhibitors.</abstract><cop>England</cop><pmid>15262246</pmid><doi>10.1016/j.joca.2004.05.002</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Osteoarthritis and cartilage, 2004-08, Vol.12 (8), p.658-666 |
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| subjects | Aged Culture Techniques Cyclooxygenase 1 Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors - pharmacology Dinoprostone - metabolism Dose-Response Relationship, Drug Female Humans Isoenzymes - antagonists & inhibitors Isoenzymes - metabolism Isoenzymes - physiology Male Membrane Proteins Middle Aged Osteoarthritis, Knee - enzymology Osteoarthritis, Knee - metabolism Osteoarthritis, Knee - pathology Prostaglandin-Endoperoxide Synthases - metabolism Prostaglandin-Endoperoxide Synthases - physiology Severity of Illness Index Synovial Membrane - drug effects Synovial Membrane - enzymology Synovitis - enzymology Synovitis - metabolism Synovitis - pathology |
| title | Participation of cyclooxygenase-1 in prostaglandin E2 release from synovitis tissue in primary osteoarthritis in vitro |
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