Inhibition of 5-lipoxygenase induces cell death in anti-inflammatory fatty acid-treated HL-60 cells

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Abstract

Background: Enteral nutrition containing eicosapentaenoic (20:5 ω-3) and γ-linolenic acid (18:3 ω-6) decreases leukotriene B4 levels and neutrophils in bronchoalveolar lavage fluid of patients and animals with acute respiratory distress syndrome. Reduction in pulmonary inflammation may be caused by decreased neutrophil migration or survival. We showed that apoptosis increases in eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. We hypothesize that eicosapentaenoic/γ-linolenic acid-induced apoptosis involves downstream metabolic products of lipoxygenase and cyclooxygenase enzymes. This study determined the effects of inhibitors of lipoxygenase and cyclooxygenase enzymes on eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. Methods: Cells were incubated with 50 μM eicosapentaenoic/20 μM γ-linolenic acid in the presence of an enzyme inhibitor (1-10 μM) for 12 hours. Compounds were used to inhibit cyclooxygenase (ibuprofen), 12-lipoxygenase (baicalein), or 5-lipoxygenase (AA-861). Flow cytometry assessed viability, apoptosis, and necrosis. Results: 5-Lipoxygenase inhibition decreased cell viability and increased cell death (apoptosis + necrosis) in eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. Inhibition of cyclooxygenase 1 and 2 and 12-lipoxygenase had no significant effect on cellular viability and death in eicosapentaenoic/γ/- linolenie acid-treated HL-60 cells. Adding leukotriene B4 counteracted the effect of 5-lipoxygenase inhibition on apoptosis in eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. Conclusions: These data suggest that the processing of eicosapentaenoic and γ-linolenic acid by 5-lipoxygenase is critical to HL-60 cell survival.

Original languageEnglish (US)
Pages (from-to)308-314
Number of pages7
JournalJournal of Parenteral and Enteral Nutrition
Volume28
Issue number5
DOIs
StatePublished - Jan 1 2004

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Arachidonate 5-Lipoxygenase
alpha-Linolenic Acid
HL-60 Cells
Cell Death
Anti-Inflammatory Agents
Fatty Acids
Apoptosis
Arachidonate 12-Lipoxygenase
Leukotriene B4
Prostaglandin-Endoperoxide Synthases
Cell Survival
Neutrophils
Necrosis
Lipoxygenase Inhibitors
Cyclooxygenase 1
Eicosapentaenoic Acid
Lipoxygenase
Cyclooxygenase Inhibitors
Ibuprofen
Adult Respiratory Distress Syndrome

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

@article{863796c243b645298cd29f3c5f36e50b,
title = "Inhibition of 5-lipoxygenase induces cell death in anti-inflammatory fatty acid-treated HL-60 cells",
abstract = "Background: Enteral nutrition containing eicosapentaenoic (20:5 ω-3) and γ-linolenic acid (18:3 ω-6) decreases leukotriene B4 levels and neutrophils in bronchoalveolar lavage fluid of patients and animals with acute respiratory distress syndrome. Reduction in pulmonary inflammation may be caused by decreased neutrophil migration or survival. We showed that apoptosis increases in eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. We hypothesize that eicosapentaenoic/γ-linolenic acid-induced apoptosis involves downstream metabolic products of lipoxygenase and cyclooxygenase enzymes. This study determined the effects of inhibitors of lipoxygenase and cyclooxygenase enzymes on eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. Methods: Cells were incubated with 50 μM eicosapentaenoic/20 μM γ-linolenic acid in the presence of an enzyme inhibitor (1-10 μM) for 12 hours. Compounds were used to inhibit cyclooxygenase (ibuprofen), 12-lipoxygenase (baicalein), or 5-lipoxygenase (AA-861). Flow cytometry assessed viability, apoptosis, and necrosis. Results: 5-Lipoxygenase inhibition decreased cell viability and increased cell death (apoptosis + necrosis) in eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. Inhibition of cyclooxygenase 1 and 2 and 12-lipoxygenase had no significant effect on cellular viability and death in eicosapentaenoic/γ/- linolenie acid-treated HL-60 cells. Adding leukotriene B4 counteracted the effect of 5-lipoxygenase inhibition on apoptosis in eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. Conclusions: These data suggest that the processing of eicosapentaenoic and γ-linolenic acid by 5-lipoxygenase is critical to HL-60 cell survival.",
author = "Gillis, {Robert C.} and Brian Daley and Blaine Enderson and Michael Karlstad",
year = "2004",
month = "1",
day = "1",
doi = "10.1177/0148607104028005308",
language = "English (US)",
volume = "28",
pages = "308--314",
journal = "Journal of Parenteral and Enteral Nutrition",
issn = "0148-6071",
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number = "5",

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TY - JOUR

T1 - Inhibition of 5-lipoxygenase induces cell death in anti-inflammatory fatty acid-treated HL-60 cells

AU - Gillis, Robert C.

AU - Daley, Brian

AU - Enderson, Blaine

AU - Karlstad, Michael

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Background: Enteral nutrition containing eicosapentaenoic (20:5 ω-3) and γ-linolenic acid (18:3 ω-6) decreases leukotriene B4 levels and neutrophils in bronchoalveolar lavage fluid of patients and animals with acute respiratory distress syndrome. Reduction in pulmonary inflammation may be caused by decreased neutrophil migration or survival. We showed that apoptosis increases in eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. We hypothesize that eicosapentaenoic/γ-linolenic acid-induced apoptosis involves downstream metabolic products of lipoxygenase and cyclooxygenase enzymes. This study determined the effects of inhibitors of lipoxygenase and cyclooxygenase enzymes on eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. Methods: Cells were incubated with 50 μM eicosapentaenoic/20 μM γ-linolenic acid in the presence of an enzyme inhibitor (1-10 μM) for 12 hours. Compounds were used to inhibit cyclooxygenase (ibuprofen), 12-lipoxygenase (baicalein), or 5-lipoxygenase (AA-861). Flow cytometry assessed viability, apoptosis, and necrosis. Results: 5-Lipoxygenase inhibition decreased cell viability and increased cell death (apoptosis + necrosis) in eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. Inhibition of cyclooxygenase 1 and 2 and 12-lipoxygenase had no significant effect on cellular viability and death in eicosapentaenoic/γ/- linolenie acid-treated HL-60 cells. Adding leukotriene B4 counteracted the effect of 5-lipoxygenase inhibition on apoptosis in eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. Conclusions: These data suggest that the processing of eicosapentaenoic and γ-linolenic acid by 5-lipoxygenase is critical to HL-60 cell survival.

AB - Background: Enteral nutrition containing eicosapentaenoic (20:5 ω-3) and γ-linolenic acid (18:3 ω-6) decreases leukotriene B4 levels and neutrophils in bronchoalveolar lavage fluid of patients and animals with acute respiratory distress syndrome. Reduction in pulmonary inflammation may be caused by decreased neutrophil migration or survival. We showed that apoptosis increases in eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. We hypothesize that eicosapentaenoic/γ-linolenic acid-induced apoptosis involves downstream metabolic products of lipoxygenase and cyclooxygenase enzymes. This study determined the effects of inhibitors of lipoxygenase and cyclooxygenase enzymes on eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. Methods: Cells were incubated with 50 μM eicosapentaenoic/20 μM γ-linolenic acid in the presence of an enzyme inhibitor (1-10 μM) for 12 hours. Compounds were used to inhibit cyclooxygenase (ibuprofen), 12-lipoxygenase (baicalein), or 5-lipoxygenase (AA-861). Flow cytometry assessed viability, apoptosis, and necrosis. Results: 5-Lipoxygenase inhibition decreased cell viability and increased cell death (apoptosis + necrosis) in eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. Inhibition of cyclooxygenase 1 and 2 and 12-lipoxygenase had no significant effect on cellular viability and death in eicosapentaenoic/γ/- linolenie acid-treated HL-60 cells. Adding leukotriene B4 counteracted the effect of 5-lipoxygenase inhibition on apoptosis in eicosapentaenoic/γ-linolenic acid-treated HL-60 cells. Conclusions: These data suggest that the processing of eicosapentaenoic and γ-linolenic acid by 5-lipoxygenase is critical to HL-60 cell survival.

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U2 - 10.1177/0148607104028005308

DO - 10.1177/0148607104028005308

M3 - Article

VL - 28

SP - 308

EP - 314

JO - Journal of Parenteral and Enteral Nutrition

JF - Journal of Parenteral and Enteral Nutrition

SN - 0148-6071

IS - 5

ER -