Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-2-12
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1733-40
pubmed:dateRevised
2007-11-15
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
pubmed:year
1998
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.
pubmed:affiliation
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't