Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-3-9
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1080-7683
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
65-74
pubmed:dateRevised
2008-11-21
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
pubmed:year
2004
pubmed:articleTitle
Retinoic acid induces corneal epithelial CYP4B1 gene expression and stimulates the synthesis of inflammatory 12-hydroxyeicosanoids.
pubmed:affiliation
Department of Pharmacology and Ophthalmology, New York Medical College, Valhalla, NY 10595, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.