Source:http://linkedlifedata.com/resource/pubmed/id/15006160
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2004-3-9
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pubmed:abstractText |
Injury to the ocular surface provokes an inflammatory response that is mediated, at least in part, by corneal epithelial derived 12-hydroxyeicosanoids (HETEs) including 12-HETE and 12-HETrE; both metabolites exhibit potent inflammatory and angiogenic properties and are formed by a cytochrome P450 (CYP) 4B1. Retinoids are known to mediate wound-healing processes in many tissues and, as such, are integral components of the inflammatory response. We studied the effect of various retinoids on corneal synthesis of 12-hydroxyeicosanoids and on activation of CYP4B1 gene expression. Corneal organ cultures were used to assess the effect of retinoic acid on epithelial metabolism of arachidonic acid to 12-hydroxyeicosanoids. Luciferase reporter vectors containing different lengths of the CYP4B1 3.4 kb-5'-untranslated region were used to examine the effect of vitamin D and retinoids (9-cis-retinoic acid and all-trans retinoic acid) on transcriptional activation of CYP4B1 in transient transfection experiments with HepG2 cells. Vitamin D had no effect on CYP4B1 promoter activity, but 9-cis and all-trans retinoic acids increased promoter activity by up to 70% over control. Addition of both 9-cis and all-trans retinoic acids resulted in an additive effect increasing promoter activity by 2-fold. The increased promoter activity correlated with the presence of RAR/RXR binding motifs. Incubation of corneal organ culture for 24 hours in the presence of 9-cis and all-trans retinoic acids increased the synthesis of 12-HETE and 12-HETrE by 2-fold. The finding that retinoic acid increases the expression of the CYP4B1 gene and enhances production of the inflammatory 12-hydroxyeicosanoids in the corneal epithelium may provide a linkage between wound healing and inflammation in the ocular surface.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyeicosatetraenoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin D,
http://linkedlifedata.com/resource/pubmed/chemical/alitretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/cytochrome P-450 CYP4B1
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1080-7683
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
65-74
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15006160-Animals,
pubmed-meshheading:15006160-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:15006160-Cell Line, Tumor,
pubmed-meshheading:15006160-Epithelium, Corneal,
pubmed-meshheading:15006160-Female,
pubmed-meshheading:15006160-Gene Expression,
pubmed-meshheading:15006160-Humans,
pubmed-meshheading:15006160-Hydroxyeicosatetraenoic Acids,
pubmed-meshheading:15006160-Luciferases,
pubmed-meshheading:15006160-Male,
pubmed-meshheading:15006160-Organ Culture Techniques,
pubmed-meshheading:15006160-Oxygen,
pubmed-meshheading:15006160-Plasmids,
pubmed-meshheading:15006160-Polymerase Chain Reaction,
pubmed-meshheading:15006160-Promoter Regions, Genetic,
pubmed-meshheading:15006160-Rabbits,
pubmed-meshheading:15006160-Transcriptional Activation,
pubmed-meshheading:15006160-Tretinoin,
pubmed-meshheading:15006160-Vitamin D
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pubmed:year |
2004
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pubmed:articleTitle |
Retinoic acid induces corneal epithelial CYP4B1 gene expression and stimulates the synthesis of inflammatory 12-hydroxyeicosanoids.
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pubmed:affiliation |
Department of Pharmacology and Ophthalmology, New York Medical College, Valhalla, NY 10595, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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