Resolvin E1 receptor activation signals phosphorylation and phagocytosis

Taisuke Ohira, Makoto Arita, Kazuhiro Omori, Antonio Recchiuti, Thomas E. Van Dykeand, Charles N. Serhan

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Resolvins are endogenous lipid mediators that actively regulate the resolution of acute inflammation. Resolvin E1 (RvE1; (5S,12R,18R)-trihydroxy-6Z, 8E,10E,14Z,16E-eicosapentaenoic acid) is an endogenous anti-inflammatory and pro-resolving mediator derived from eicosapentaenoic acid that regulates leukocyte migration and enhances macrophage phagocytosis of apoptotic neutrophils to resolve inflammation. In the inflammatory milieu, RvE1 mediates counter-regulatory actions initiated via specific G protein-coupled receptors. Here, we have identified RvE1-specific signaling pathways initiated by the RvE1 receptor ChemR23. RvE1 stimulated phosphorylation of Akt that was both ligand- and receptor-dependent. RvE1 regulated Akt phosphorylation in a time (0-15 min)- and dose-dependent (0.01-100 nM) manner in human ChemR23-transfected Chinese hamster ovary cells. RvE1 stimulated phosphorylation of both Akt and a 30-kDa protein, a downstream target of Akt, identified using a phospho-Akt substrate antibody. The 30-kDa protein was identified as ribosomal protein S6, a translational regulator, and its phosphorylation was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor (wortmannin) and an ERK inhibitor (PD98059) but not by a p38-MAPK inhibitor (SB203580). Ribosomal protein S6 is a downstream target of the PI3K/Akt signaling pathway as well as the Raf/ERK pathway. In ChemR23-expressing differentiated HL60 cells, RvE1 also stimulated the phosphorylation of ribosomal protein S6. In addition, RvE1 enhanced phagocytosis of zymosanAby human macrophages, which are inhibited by PD98059 and rapamycin (mTOR inhibitor). These results indicate that RvE1 initiates direct activation of ChemR23 and signals receptor-dependent phosphorylation. These phosphorylation-signaling pathways identified for RvE1 receptor-ligand interactions underscore the importance of endogenous pro-resolving agonists in resolving acute inflammation.

Original languageEnglish
Pages (from-to)3451-3461
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number5
DOIs
Publication statusPublished - Jan 29 2010
Externally publishedYes

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Phosphorylation
Phagocytosis
Chemical activation
Ribosomal Protein S6
Phosphatidylinositol 3-Kinase
Macrophages
Inflammation
5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid
Ligands
Eicosapentaenoic Acid
MAP Kinase Signaling System
HL-60 Cells
p38 Mitogen-Activated Protein Kinases
Sirolimus
G-Protein-Coupled Receptors
Cricetulus
Ovary
Proteins
Neutrophils
Leukocytes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Ohira, T., Arita, M., Omori, K., Recchiuti, A., Van Dykeand, T. E., & Serhan, C. N. (2010). Resolvin E1 receptor activation signals phosphorylation and phagocytosis. Journal of Biological Chemistry, 285(5), 3451-3461. https://doi.org/10.1074/jbc.M109.044131

Resolvin E1 receptor activation signals phosphorylation and phagocytosis. / Ohira, Taisuke; Arita, Makoto; Omori, Kazuhiro; Recchiuti, Antonio; Van Dykeand, Thomas E.; Serhan, Charles N.

In: Journal of Biological Chemistry, Vol. 285, No. 5, 29.01.2010, p. 3451-3461.

Research output: Contribution to journalArticle

Ohira, T, Arita, M, Omori, K, Recchiuti, A, Van Dykeand, TE & Serhan, CN 2010, 'Resolvin E1 receptor activation signals phosphorylation and phagocytosis', Journal of Biological Chemistry, vol. 285, no. 5, pp. 3451-3461. https://doi.org/10.1074/jbc.M109.044131
Ohira, Taisuke ; Arita, Makoto ; Omori, Kazuhiro ; Recchiuti, Antonio ; Van Dykeand, Thomas E. ; Serhan, Charles N. / Resolvin E1 receptor activation signals phosphorylation and phagocytosis. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 5. pp. 3451-3461.
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