Characterization of prostaglandin E 2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophils

Mireille St-Onge, Nicolas Flamand, Jordane Biarc, Serge Picard, Line Bouchard, Andrée Anne Dussault, Cynthia Laflamme, Michael J. James, Gillian Caughey, Leslie G. Cleland, Pierre Borgeat, Marc Pouliot

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

In the present study, we characterized the generation of prostaglandin (PG)E 2 in human neutrophils. We found that the Ca 2+ -dependent type IV cytosolic phospholipase A 2 (cPLA 2 ) was pivotally involved in the COX-2-mediated generation of PGE 2 in response to a calcium ionophore, as determined by the use of selected PLA 2 inhibitors. PGE 2 biosynthesis elicited by bacterial-derived peptides or by phagocytic stimuli acting on cell surface receptors also showed to be dependent on cPLA 2 activity. We then assessed metabolism of unesterified arachidonic acid (AA), and observed that PGE 2 production becomes favored over that of LTB 4 with higher AA concentrations. Withdrawal of calcium prevented the generation of PGE 2 in response to a calcium ionophore but did not affect the up-regulation of COX-2 or its capacity to convert AA, thus limiting its implication at the level of cPLA 2 activation. Of the main eicosanoids produced by neutrophils, only LTB 4 was able to up-regulate COX-2 expression. Finally, the only PGE synthase isoform found in neutrophils is microsomal PGE synthase-1; it co-localized with COX-2 and its expression appeared mainly constitutive. These results highlight key differences in regulatory processes of the 5-LO and COX pathways, and enhance our knowledge at several levels in the PGE 2 biosynthesis in neutrophils.

LanguageEnglish
Pages1235-1245
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1771
Issue number9
DOIs
Publication statusPublished - 1 Sep 2007
Externally publishedYes

Keywords

  • Cyclooxygenase
  • Eicosanoids
  • Fatty acid
  • Inflammation
  • Polymorphonuclear leukocyte
  • Prostaglandins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

St-Onge, Mireille ; Flamand, Nicolas ; Biarc, Jordane ; Picard, Serge ; Bouchard, Line ; Dussault, Andrée Anne ; Laflamme, Cynthia ; James, Michael J. ; Caughey, Gillian ; Cleland, Leslie G. ; Borgeat, Pierre ; Pouliot, Marc. / Characterization of prostaglandin E 2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophils In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. 2007 ; Vol. 1771, No. 9. pp. 1235-1245.
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abstract = "In the present study, we characterized the generation of prostaglandin (PG)E 2 in human neutrophils. We found that the Ca 2+ -dependent type IV cytosolic phospholipase A 2 (cPLA 2 ) was pivotally involved in the COX-2-mediated generation of PGE 2 in response to a calcium ionophore, as determined by the use of selected PLA 2 inhibitors. PGE 2 biosynthesis elicited by bacterial-derived peptides or by phagocytic stimuli acting on cell surface receptors also showed to be dependent on cPLA 2 activity. We then assessed metabolism of unesterified arachidonic acid (AA), and observed that PGE 2 production becomes favored over that of LTB 4 with higher AA concentrations. Withdrawal of calcium prevented the generation of PGE 2 in response to a calcium ionophore but did not affect the up-regulation of COX-2 or its capacity to convert AA, thus limiting its implication at the level of cPLA 2 activation. Of the main eicosanoids produced by neutrophils, only LTB 4 was able to up-regulate COX-2 expression. Finally, the only PGE synthase isoform found in neutrophils is microsomal PGE synthase-1; it co-localized with COX-2 and its expression appeared mainly constitutive. These results highlight key differences in regulatory processes of the 5-LO and COX pathways, and enhance our knowledge at several levels in the PGE 2 biosynthesis in neutrophils.",
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St-Onge, M, Flamand, N, Biarc, J, Picard, S, Bouchard, L, Dussault, AA, Laflamme, C, James, MJ, Caughey, G, Cleland, LG, Borgeat, P & Pouliot, M 2007, ' Characterization of prostaglandin E 2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophils ', Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, vol. 1771, no. 9, pp. 1235-1245. https://doi.org/10.1016/j.bbalip.2007.06.002

Characterization of prostaglandin E 2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophils . / St-Onge, Mireille; Flamand, Nicolas; Biarc, Jordane; Picard, Serge; Bouchard, Line; Dussault, Andrée Anne; Laflamme, Cynthia; James, Michael J.; Caughey, Gillian; Cleland, Leslie G.; Borgeat, Pierre; Pouliot, Marc.

In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1771, No. 9, 01.09.2007, p. 1235-1245.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Characterization of prostaglandin E 2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophils

AU - St-Onge, Mireille

AU - Flamand, Nicolas

AU - Biarc, Jordane

AU - Picard, Serge

AU - Bouchard, Line

AU - Dussault, Andrée Anne

AU - Laflamme, Cynthia

AU - James, Michael J.

AU - Caughey, Gillian

AU - Cleland, Leslie G.

AU - Borgeat, Pierre

AU - Pouliot, Marc

PY - 2007/9/1

Y1 - 2007/9/1

N2 - In the present study, we characterized the generation of prostaglandin (PG)E 2 in human neutrophils. We found that the Ca 2+ -dependent type IV cytosolic phospholipase A 2 (cPLA 2 ) was pivotally involved in the COX-2-mediated generation of PGE 2 in response to a calcium ionophore, as determined by the use of selected PLA 2 inhibitors. PGE 2 biosynthesis elicited by bacterial-derived peptides or by phagocytic stimuli acting on cell surface receptors also showed to be dependent on cPLA 2 activity. We then assessed metabolism of unesterified arachidonic acid (AA), and observed that PGE 2 production becomes favored over that of LTB 4 with higher AA concentrations. Withdrawal of calcium prevented the generation of PGE 2 in response to a calcium ionophore but did not affect the up-regulation of COX-2 or its capacity to convert AA, thus limiting its implication at the level of cPLA 2 activation. Of the main eicosanoids produced by neutrophils, only LTB 4 was able to up-regulate COX-2 expression. Finally, the only PGE synthase isoform found in neutrophils is microsomal PGE synthase-1; it co-localized with COX-2 and its expression appeared mainly constitutive. These results highlight key differences in regulatory processes of the 5-LO and COX pathways, and enhance our knowledge at several levels in the PGE 2 biosynthesis in neutrophils.

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KW - Cyclooxygenase

KW - Eicosanoids

KW - Fatty acid

KW - Inflammation

KW - Polymorphonuclear leukocyte

KW - Prostaglandins

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DO - 10.1016/j.bbalip.2007.06.002

M3 - Article

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SP - 1235

EP - 1245

JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

T2 - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

SN - 1388-1981

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ER -