Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-6-27
pubmed:abstractText
Synthetic and natural melanocortin (MC) peptides afford inhibitory properties in inflammation and tissue injury, but characterization of receptor involvement is still elusive. We used the agonist AP214 to test MC-dependent anti-inflammatory effects. In zymosan peritonitis, treatment of mice with AP214 (400 to 800 ?g/kg) inhibited cell infiltration, an effect retained in MC receptor type 1, or MC(1), mutant mice but lost in MC(3) null mice. In vitro, cytokine release from zymosan-stimulated macrophages was affected by AP214, with approximately 80%, 30%, and 40% reduction in IL-1?, tumor necrosis factor-?, and IL-6, respectively. Inhibition of IL-1? release was retained in MC(1) mutant cells but was lost in MC(3) null cells. Furthermore, AP214 augmented uptake of zymosan particles and human apoptotic neutrophils by wild-type macrophages: this proresolving property was lost in MC(3) null macrophages. AP214 displayed its pro-efferocytotic effect also in vivo. Finally, in a model of inflammatory arthritis, AP214 evoked significant reductions in the clinical score. These results indicate that AP214 elicits anti-inflammatory responses, with a preferential effect on IL-1? release. Furthermore, we describe for the first time a positive modulation of an MC agonist on the process of efferocytosis. In all cases, endogenous MC(3) is the receptor that mediates these novel properties of AP214. These findings might clarify the tissue-protective properties of AP214 in clinical settings and may open further development for novel MC agonists.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1525-2191
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
179
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
259-69
pubmed:meshHeading
pubmed-meshheading:21703408-Animals, pubmed-meshheading:21703408-Apoptosis, pubmed-meshheading:21703408-Arthritis, Experimental, pubmed-meshheading:21703408-Blotting, Western, pubmed-meshheading:21703408-Cytokines, pubmed-meshheading:21703408-Disease Models, Animal, pubmed-meshheading:21703408-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:21703408-Humans, pubmed-meshheading:21703408-Inflammation, pubmed-meshheading:21703408-Interleukin-1beta, pubmed-meshheading:21703408-Interleukin-6, pubmed-meshheading:21703408-Macrophages, pubmed-meshheading:21703408-Macrophages, Peritoneal, pubmed-meshheading:21703408-Male, pubmed-meshheading:21703408-Melanocortins, pubmed-meshheading:21703408-Mice, pubmed-meshheading:21703408-Mice, Inbred C57BL, pubmed-meshheading:21703408-Mice, Knockout, pubmed-meshheading:21703408-Mutation, pubmed-meshheading:21703408-Neutrophils, pubmed-meshheading:21703408-Peritonitis, pubmed-meshheading:21703408-Phagocytosis, pubmed-meshheading:21703408-RNA, Messenger, pubmed-meshheading:21703408-Receptor, Melanocortin, Type 1, pubmed-meshheading:21703408-Receptor, Melanocortin, Type 3, pubmed-meshheading:21703408-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21703408-Tumor Necrosis Factor-alpha, pubmed-meshheading:21703408-alpha-MSH
pubmed:year
2011
pubmed:articleTitle
The melanocortin agonist AP214 exerts anti-inflammatory and proresolving properties.
pubmed:affiliation
The William Harvey Research Institute, Barts, and The London School of Medicine, Queen Mary University of London, London, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't