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Identification of specialized pro-resolving mediator clusters from healthy adults after intravenous low-dose endotoxin and omega-3 supplementation: a methodological validation

Norris PC, Skulas-Ray AC, Riley I, Richter CK, Kris-Etherton PM, Jensen GL, Serhan CN, Maddipati KR

Scientific reports · 99 citas

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Quién lo pagó

Financiación
Financiación independiente
Gobierno
U.S. Department of Agriculture
Universidad u hospital
University of Pennsylvania
Universidad u hospital
Pennsylvania State University
Universidad u hospital
Georgia Clinical and Translational Science Alliance
Gobierno
National Institutes of Health
Gobierno
Cooperative State Research, Education, and Extension Service
Gobierno
National Institute of General Medical Sciences
Gobierno
National Center for Research Resources
Gobierno
National Center for Advancing Translational Sciences
Gobierno
NCRR NIH HHS
Gobierno
NCATS NIH HHS
Gobierno
NIGMS NIH HHS
Subvenciones
National Center for Advancing Translational Sciences (UL1-TR000127); Pennsylvania State University (UL1TR000127); National Institute of General Medical Sciences (P01GM095467); National Center for Advancing Translational Sciences (TR000127); National Center for Research Resources (S10-RR-027926); National Center for Research Resources (M01-RR-010732); National Institutes of Health (M01-RR-10-732); National Institutes of Health (1s10rr027926-01); Pennsylvania State University (NIH/NCATS Grant Number UL1 TR000127); National Institutes of Health (TR000127); National Institutes of Health (UL1-TR-000127)

Según 12 financiadores declarados y la declaración de financiación del texto completo.

Publicación

Publicado
2018-12-17 · Sci Rep · vol. 8 · número 1 · pág. 18050
Editorial
Nature Portfolio
Citado
103 citas · más que el 97% de estudios similares · 6.3× el promedio de su campo
Impacto
Entre el 10 % más citado de su campo
Referencias
61 trabajos
Acceso
Acceso abierto (revista) · CC-BY
Áreas de investigación
Fatty Acid Research and Health · Eicosanoids and Hypertension Pharmacology · Metabolomics and Mass Spectrometry Studies
Palabras clave
specialized pro-resolving mediators, omega-3 fatty acids, eicosapentaenoic acid, docosahexaenoic acid, resolvins, lipoxins, lipopolysaccharide challenge, endotoxin, inflammation resolution, interlaboratory validation, prostaglandins, thromboxane
MeSH
humans, inflammation, fatty acids, omega-3, docosahexaenoic acids, eicosapentaenoic acid, endotoxins, chromatography, liquid, dose-response relationship, drug, research design, dietary supplements, adult, female, male, lipid metabolism, tandem mass spectrometry, metabolomics, metabolome, young adult, administration, intravenous, healthy volunteers

8 autores

  • Paul C. Norris🇺🇸Brigham and Women's Hospital; Harvard University
  • Ann C. Skulas‐Ray🇺🇸University of Arizona
  • Ian R. Riley🇺🇸Brigham and Women's Hospital; Harvard University
  • Chesney K. Richter🇺🇸University of Arizona
  • Penny M. Kris‐Etherton🇺🇸Pennsylvania State University
  • Gordon Lee Jensen🇺🇸University of Vermont
  • Charles Nicholas Serhan🇺🇸 · autor de correspondenciaBrigham and Women's Hospital; Harvard University
  • Krishna Rao Maddipati🇺🇸 · autor de correspondenciaWayne State University

Resumen

El texto original del estudio, en el idioma en que se publicó.

Specialized pro-resolving mediator(s) (SPMs) are produced from the endogenous ω-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and accelerate resolution of acute inflammation. We identified specific clusters of SPM in human plasma and serum using LC-MS/MS based lipid mediator (LM) metabololipidomics in two separate laboratories for inter-laboratory validation. The human plasma cluster consisted of resolvin (Rv)E1, RvD1, lipoxin (LX)B4, 18-HEPE, and 17-HDHA, and the human serum cluster consisted of RvE1, RvD1, AT-LXA4, 18-HEPE, and 17-HDHA. Human plasma and serum SPM clusters were increased after ω-3 supplementation (triglyceride dietary supplements or prescription ethyl esters) and low dose intravenous lipopolysaccharide (LPS) challenge. These results were corroborated by parallel determinations with the same coded samples in a second, separate laboratory using essentially identical metabololipidomic operational parameters. In these healthy subjects, two ω-3 supplementation protocols (Study A and Study B) temporally increased the SPM cluster throughout the endotoxin-challenge time course. Study A and Study B were randomized and Study B also had a crossover design with placebo and endotoxin challenge. Endotoxin challenge temporally regulated lipid mediator production in human serum, where pro-inflammatory eicosanoid (prostaglandins and thromboxane) concentrations peaked by 8 hours post-endotoxin and SPMs such as resolvins and lipoxins initially decreased by 2 h and were then elevated at 24 hours. In healthy adults given ω-3 supplementation, the plasma concentration of the SPM cluster (RvE1, RvD1, LXB4, 18-HEPE, and 17-HDHA) peaked at two hours post endotoxin challenge. These results from two separate laboratories with the same samples provide evidence for temporal production of specific pro-resolving mediators with ω-3 supplementation that together support the role of SPM in vivo in inflammation-resolution in humans.

Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).

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