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Inflammatory Response

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Analysis of Raw and Processed Cyperi Rhizoma Samples Using Liquid Chromatography-Tandem Mass Spectrometry in Rats with Primary Dysmenorrhea
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CYP450-derived oxylipins mediate inflammatory resolution.

Derek W Gilroy1, Matthew L Edin2, Roel P H De Maeyer3

  • 1Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, University College London, London WC1E 6JJ, United Kingdom; d.gilroy@ucl.ac.uk dbishopbailey@rvc.ac.uk.

Proceedings of the National Academy of Sciences of the United States of America
|May 27, 2016
PubMed
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Epoxy-oxylipins regulate immune cell activity during inflammation resolution. Inhibiting their production increases specific monocytes and impairs macrophage function, revealing a novel regulatory system for adaptive immunity.

Keywords:
epoxygenasemonocyteoxylipinsphagocytosisresolution

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Area of Science:

  • Immunobiology
  • Lipid mediators
  • Inflammation resolution

Background:

  • Resolution of inflammation is an active immune process.
  • Mononuclear phagocytes are key in efferocytosis and bridging innate and adaptive immunity.
  • Cytochrome P450 (CYP)-derived epoxy-oxylipins' role in resolution is unclear.

Purpose of the Study:

  • Investigate the role of CYP-derived epoxy-oxylipins in sterile peritonitis resolution.
  • Determine how epoxy-oxylipins influence immune cell recruitment and function during resolution.

Main Methods:

  • Used a mouse model of sterile resolving peritonitis.
  • Administered an epoxygenase inhibitor (SKF525A, epoxI) at 24h.
  • Analyzed immune cell populations (monocytes, macrophages, T cells, B cells, dendritic cells) and their markers (GR1, Ly6c, CCR2, F4/80, CD11b, MerTK, CD103).
  • Assessed phagocytosis and efferocytosis ex vivo.

Main Results:

  • Epoxy-oxylipins were produced in two phases during inflammation resolution.
  • Inhibiting epoxygenase (epoxI) increased specific monocyte influx (GR1+, Ly6c(hi), CCR2(hi)) and suppressed other immune cells.
  • Mice lacking soluble epoxide hydrolase (sEH-/-) showed opposite effects with reduced Ly6c(hi) monocytes and increased macrophages and adaptive immune cells.
  • EpoxI treatment impaired macrophage differentiation markers and phagocytic/efferocytic capacity.
  • Immune cell resolution signatures were altered by epoxI treatment.

Conclusions:

  • Epoxy-oxylipins are critical for regulating monocyte recruitment and activity during inflammatory resolution.
  • These lipid mediators represent a previously unknown regulatory system for adaptive immunity establishment.
  • Targeting epoxy-oxylipin pathways may offer novel therapeutic strategies for inflammatory diseases.