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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0012472,
umls-concept:C0016030,
umls-concept:C0017262,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0079411,
umls-concept:C0086597,
umls-concept:C0185117,
umls-concept:C0205421,
umls-concept:C0332307,
umls-concept:C1333201,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C2698651,
umls-concept:C2756983,
umls-concept:C2911684
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pubmed:issue |
3
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pubmed:dateCreated |
1998-2-12
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pubmed:abstractText |
Activation of rat fibroblastic 3Y1 cells with interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) induced delayed prostaglandin (PG) E2 generation over 6-48 h, which occurred in parallel with de novo induction of type IIA secretory phospholipase A2 (sPLA2) and cyclooxygenase (COX)-2, without accompanied by changes in the constitutive expression of type IV cytosolic PLA2 (cPLA2) and COX-1. Types V and IIC sPLA2s were barely detectable in these cells. Studies using an anti-type IIA sPLA2 antibody, sPLA2 inhibitors, and a type IIA sPLA2-specific antisense oligonucleotide revealed that IL-1 beta/TNF alpha-induced delayed PGE2 generation by these cells was largely dependent on inducible type IIA sPLA2, which was functionally linked to inducible COX-2. Delayed PGE2 generation was also suppressed markedly by the cPLA2 inhibitor arachidonoyl trifluoromethyl ketone (AACOCF3), which attenuated induction of type IIA sPLA2, but not COX-2, expression. AACOCF3 inhibited the initial phase of cytokine-stimulated arachidonic acid release, and supplementing AACOCF3-treated cells with exogenous arachidonic acid partially restored type IIA sPLA2 expression. These results suggest that certain metabolites produced by the cPLA2-dependent pathway are crucial for the subsequent induction of type IIA sPLA2 expression and attendant delayed PGE2 generation. Some lipoxygenase-derived products might be involved in this event, since IL-1 beta/TNF alpha-induced type IIA sPLA2 induction and PGE2 generation were reduced markedly by lipoxygenase, but not COX, inhibitors. In contrast, Ca2+ ionophore-stimulated immediate PGE2 generation was regulated predominantly by the constitutive enzymes cPLA2 and COX-1, even when type IIA sPLA2 and COX-2 were maximally induced after IL-1 beta/TNF alpha treatment, revealing functional segregation of the constitutive and inducible PG biosynthetic enzymes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcimycin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Ionophores,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
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/Ptgs1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1733-40
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9430720-Animals,
pubmed-meshheading:9430720-Calcimycin,
pubmed-meshheading:9430720-Cell Line,
pubmed-meshheading:9430720-Cyclooxygenase 1,
pubmed-meshheading:9430720-Cyclooxygenase 2,
pubmed-meshheading:9430720-Cytokines,
pubmed-meshheading:9430720-Cytosol,
pubmed-meshheading:9430720-Dinoprostone,
pubmed-meshheading:9430720-Enzyme Activation,
pubmed-meshheading:9430720-Fibroblasts,
pubmed-meshheading:9430720-Ionophores,
pubmed-meshheading:9430720-Isoenzymes,
pubmed-meshheading:9430720-Membrane Proteins,
pubmed-meshheading:9430720-Molecular Weight,
pubmed-meshheading:9430720-Oligonucleotides, Antisense,
pubmed-meshheading:9430720-Phospholipases A,
pubmed-meshheading:9430720-Phospholipases A2,
pubmed-meshheading:9430720-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:9430720-Rats,
pubmed-meshheading:9430720-Tumor Necrosis Factor-alpha
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pubmed:year |
1998
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pubmed:articleTitle |
Cytosolic phospholipase A2 is required for cytokine-induced expression of type IIA secretory phospholipase A2 that mediates optimal cyclooxygenase-2-dependent delayed prostaglandin E2 generation in rat 3Y1 fibroblasts.
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pubmed:affiliation |
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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