Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
1992-11-16
pubmed:abstractText
We recently demonstrated that sphingosine enhances interleukin-1 beta (IL-1)-mediated prostaglandin E2 (PGE2) production in human dermal fibroblasts (Ballou, L. R., Barker, S. C., Postlethwaite, A. E., and Kang, A. H. (1990) J. Immunol. 145, 4245-4251). Because sphingosine and ceramide are interconvertable, we extended previous studies by treating cells with C2-ceramide (C2-cer), a membrane-soluble analogue of ceramide, and found that C2-cer stimulates IL-1-mediated PGE2 production to the same degree as sphingosine. In an effort to elucidate the mechanistic basis by which sphingosine and C2-cer affect PGE2 production, we examined the effect of these molecules on the expression of genes encoding cyclooxygenase (EC 1.14.99.1, Cox) and phospholipase A2 (EC 3.1.1.4, PLA2), the rate-limiting enzymes in PGE2 biosynthesis. We found that sphingosine and C2-cer treatment resulted in an 8-fold induction of Cox mRNA within 1-2 h which declined thereafter; concomitant changes in Cox protein were also observed. In contrast, expression of phospholipase A2 remained unaltered. We also found that IL-1-mediated PGE2 production was dramatically enhanced in cells treated simultaneously with sphingomyelinase which led us to directly test the effect of IL-1 on sphingomyelin turnover. IL-1 treatment induced the hydrolysis of a significant fraction of prelabeled sphingomyelin which was accompanied by increased levels of intracellular ceramide. Taken together, our results suggest that enhanced Cox expression may account for the observed enhancement of IL-1-mediated PGE2 production by sphingosine and C2-cer. These data also suggest that endogenous sphingomyelin metabolites, generated in response to IL-1, may play an important role in IL-1 signal transduction.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20044-50
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:1400321-Base Sequence, pubmed-meshheading:1400321-Blotting, Western, pubmed-meshheading:1400321-Cells, Cultured, pubmed-meshheading:1400321-Ceramides, pubmed-meshheading:1400321-Dinoprostone, pubmed-meshheading:1400321-Gene Expression Regulation, Enzymologic, pubmed-meshheading:1400321-Humans, pubmed-meshheading:1400321-Interleukin-1, pubmed-meshheading:1400321-Molecular Sequence Data, pubmed-meshheading:1400321-Oligonucleotides, pubmed-meshheading:1400321-Phospholipases A, pubmed-meshheading:1400321-Phospholipases A2, pubmed-meshheading:1400321-Polymerase Chain Reaction, pubmed-meshheading:1400321-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:1400321-Radioimmunoassay, pubmed-meshheading:1400321-Signal Transduction, pubmed-meshheading:1400321-Sphingomyelins, pubmed-meshheading:1400321-Sphingosine
pubmed:year
1992
pubmed:articleTitle
Interleukin-1-mediated PGE2 production and sphingomyelin metabolism. Evidence for the regulation of cyclooxygenase gene expression by sphingosine and ceramide.
pubmed:affiliation
Department of Veterans Affairs Medical Center, Memphis, Tennessee.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.