Linked Life Data

15708862

Source:http://linkedlifedata.com/resource/pubmed/id/15708862

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2005-4-11
pubmed:abstractText
The surface of the eye actively suppresses inflammation while maintaining a remarkable capacity for epithelial wound repair. Our understanding of mechanisms that balance inflammatory/reparative responses to provide effective host defense while preserving tissue function is limited, in particular, in the cornea. Lipoxin A(4) (LXA(4)) and docosahexaenoic acid-derived neuroprotectin D1 (NPD1) are lipid autacoids formed by 12/15-lipoxygenase (LOX) pathways that exhibit anti-inflammatory and neuroprotective properties. Here, we demonstrate that mouse corneas generate endogenous LXA(4) and NPD1. 12/15-LOX (Alox15) and LXA(4) receptor mRNA expression as well as LXA(4) formation were abrogated by epithelial removal and restored during wound healing. Amplification of these pathways by topical treatment with LXA(4) or NPD1 (1 microg) increased the rate of re-epithelialization (65-90%, n = 6-10, p < 0.03) and attenuated the sequelae of thermal injury. In contrast, the proinflammatory eicosanoids, LTB(4) and 12R-hydroxyeicosatrienoic acid, had no impact on corneal re-epithelialization. Epithelial removal induced a temporally defined influx of neutrophils into the stroma as well as formation of the proinflammatory chemokine KC. Topical treatment with LXA(4) and NPD1 significantly increased PMNs in the cornea while abrogating KC formation by 60%. More importantly, Alox15-deficient mice exhibited a defect in both corneal re-epithelialization and neutrophil recruitment that correlated with a 43% reduction in endogenous LXA(4) formation. Collectively, these results identify a novel action for the mouse 12/15-LOX (Alox15) and its products, LXA(4) and NPD1, in wound healing that is distinct from their well established anti-inflammatory properties.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15267-78
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15708862-Animals, pubmed-meshheading:15708862-Anti-Inflammatory Agents, pubmed-meshheading:15708862-Arachidonate 12-Lipoxygenase, pubmed-meshheading:15708862-Arachidonate 15-Lipoxygenase, pubmed-meshheading:15708862-Chemokines, pubmed-meshheading:15708862-Chromatography, High Pressure Liquid, pubmed-meshheading:15708862-Cornea, pubmed-meshheading:15708862-Docosahexaenoic Acids, pubmed-meshheading:15708862-Eicosanoids, pubmed-meshheading:15708862-Epithelial Cells, pubmed-meshheading:15708862-Epithelium, pubmed-meshheading:15708862-Gas Chromatography-Mass Spectrometry, pubmed-meshheading:15708862-Hot Temperature, pubmed-meshheading:15708862-Hydroxyeicosatetraenoic Acids, pubmed-meshheading:15708862-Inflammation, pubmed-meshheading:15708862-Leukocytes, pubmed-meshheading:15708862-Leukotriene B4, pubmed-meshheading:15708862-Lipid Metabolism, pubmed-meshheading:15708862-Mice, pubmed-meshheading:15708862-Mice, Inbred BALB C, pubmed-meshheading:15708862-Models, Chemical, pubmed-meshheading:15708862-Neutrophils, pubmed-meshheading:15708862-Phenotype, pubmed-meshheading:15708862-RNA, Messenger, pubmed-meshheading:15708862-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15708862-Time Factors, pubmed-meshheading:15708862-Ultraviolet Rays, pubmed-meshheading:15708862-Wound Healing
pubmed:year
2005
pubmed:articleTitle
A role for the mouse 12/15-lipoxygenase pathway in promoting epithelial wound healing and host defense.
pubmed:affiliation
New York Medical College, Department of Pharmacology, Valhalla, New York 10595, USA. karsten_gronert@nymc.edu <karsten_gronert@nymc.edu>
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural