Source:http://linkedlifedata.com/resource/pubmed/id/15778399
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
2005-3-21
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pubmed:abstractText |
The cellular events underlying the resolution of acute inflammation are not known in molecular terms. To identify anti-inflammatory and proresolving circuits, we investigated the temporal and differential changes in self-resolving murine exudates using mass spectrometry-based proteomics and lipidomics. Key resolution components were defined as resolution indices including Psi(max), the maximal neutrophil numbers that are present during the inflammatory response; T(max), the time when Psi(max) occurs; and the resolution interval (R(i)) from T(max) to T(50) when neutrophil numbers reach half Psi(max). The onset of resolution was at approximately 12 h with proteomic analysis showing both haptoglobin and S100A9 levels were maximal and other exudate proteins were dynamically regulated. Eicosanoids and polyunsaturated fatty acids first appeared within 4 h. Interestingly, the docosahexaenoic acid-derived anti-inflammatory lipid mediator 10,17S-docosatriene was generated during the R(i). Administration of aspirin-triggered lipoxin A(4) analog, resolvin E1, or 10,17S-docosatriene each either activated and/or accelerated resolution. For example, aspirin-triggered lipoxin A(4) analog reduced Psi(max), resolvin E1 decreased both Psi(max) and T(max), whereas 10,17S-docosatriene reduced Psi(max), T(max), and shortened R(i). Also, aspirin-triggered lipoxin A(4) analog markedly inhibited proinflammatory cytokines and chemokines at 4 h (20-50% inhibition), whereas resolvin E1 and 10,17S-docosatriene's inhibitory actions were maximal at 12 h (30-80% inhibition). Moreover, aspirin-triggered lipoxin A(4) analog evoked release of the antiphlogistic cytokine TGF-beta. These results characterize the first molecular resolution circuits and their major components activated by specific novel lipid mediators (i.e., resolvin E1 and 10,17S-docosatriene) to promote resolution.
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pubmed:grant | |
pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5S,12R,18R-trihydroxy-6Z,8E,10E,14Z...,
http://linkedlifedata.com/resource/pubmed/chemical/Calgranulin B,
http://linkedlifedata.com/resource/pubmed/chemical/Eicosanoids,
http://linkedlifedata.com/resource/pubmed/chemical/Eicosapentaenoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Haptoglobins,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
174
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4345-55
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15778399-Animals,
pubmed-meshheading:15778399-Calgranulin B,
pubmed-meshheading:15778399-Eicosanoids,
pubmed-meshheading:15778399-Eicosapentaenoic Acid,
pubmed-meshheading:15778399-Gene Expression Regulation,
pubmed-meshheading:15778399-Haptoglobins,
pubmed-meshheading:15778399-Inflammation,
pubmed-meshheading:15778399-Lipids,
pubmed-meshheading:15778399-Male,
pubmed-meshheading:15778399-Mass Spectrometry,
pubmed-meshheading:15778399-Mice,
pubmed-meshheading:15778399-Mice, Inbred Strains,
pubmed-meshheading:15778399-Neutrophils,
pubmed-meshheading:15778399-Proteins
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pubmed:year |
2005
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pubmed:articleTitle |
Molecular circuits of resolution: formation and actions of resolvins and protectins.
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pubmed:affiliation |
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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