Reactive oxygen species mediate cyclooxygenase-2 induction during monocyte to macrophage differentiation: Critical role of NADPH oxidase

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Abstract

Objective: The objective of this study was to explore the relationship between monocyte differentiation into macrophages and cyclooxygenase-2 (Cox-2) expression, based upon the observation that high amounts of this enzyme, colocalizing mainly with macrophages, have been found in human atherosclerotic lesions. Moreover, the hypothesis that reactive oxygen species (ROS) could be important as mediators of Cox-2 expression during monocyte differentiation was verified. Although ROS are known as modulators of gene expression profile, their involvement in monocyte differentiation has not been explored previously. Methods: Human adherent monocytes and the promonocytic cell line U937 were differentiated into macrophages by phorbol ester (PMA). Cox-2 was evaluated in terms of protein, mRNA and activity. Intracellular ROS formation was measured by the oxidant sensitive dye 2′,7′-dichlorofluorescein diacetate. NADPH oxidase subunit p47phox was evaluated by Western blot analysis. Results: Functionally active Cox-2 is expressed during PMA-induced monocyte transition into macrophages and ROS driven by the NADPH oxidase play a critical role in this event. Conclusion: Monocyte differentiation into macrophages, possibly triggered by unquenched ROS, may contribute to the increased inflammatory response within atheromata.

Original languageEnglish
Pages (from-to)187-197
Number of pages11
JournalCardiovascular Research
Volume60
Issue number1
DOIs
Publication statusPublished - Nov 1 2003

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NADPH Oxidase
Cyclooxygenase 2
Monocytes
Reactive Oxygen Species
Macrophages
Phorbol Esters
Atherosclerotic Plaques
Transcriptome
Oxidants
Western Blotting
Cell Line
Messenger RNA
Enzymes
Proteins

Keywords

  • Atherosclerosis
  • Free radicals
  • Infection/inflammation
  • Macrophages
  • Prostaglandins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Reactive oxygen species mediate cyclooxygenase-2 induction during monocyte to macrophage differentiation: Critical role of NADPH oxidase",
abstract = "Objective: The objective of this study was to explore the relationship between monocyte differentiation into macrophages and cyclooxygenase-2 (Cox-2) expression, based upon the observation that high amounts of this enzyme, colocalizing mainly with macrophages, have been found in human atherosclerotic lesions. Moreover, the hypothesis that reactive oxygen species (ROS) could be important as mediators of Cox-2 expression during monocyte differentiation was verified. Although ROS are known as modulators of gene expression profile, their involvement in monocyte differentiation has not been explored previously. Methods: Human adherent monocytes and the promonocytic cell line U937 were differentiated into macrophages by phorbol ester (PMA). Cox-2 was evaluated in terms of protein, mRNA and activity. Intracellular ROS formation was measured by the oxidant sensitive dye 2′,7′-dichlorofluorescein diacetate. NADPH oxidase subunit p47phox was evaluated by Western blot analysis. Results: Functionally active Cox-2 is expressed during PMA-induced monocyte transition into macrophages and ROS driven by the NADPH oxidase play a critical role in this event. Conclusion: Monocyte differentiation into macrophages, possibly triggered by unquenched ROS, may contribute to the increased inflammatory response within atheromata.",
keywords = "Atherosclerosis, Free radicals, Infection/inflammation, Macrophages, Prostaglandins",
author = "Barbieri, {Silvia Stella} and Sonia Eligini and Marta Brambilla and Elena Tremoli and Susanna Colli",
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T1 - Reactive oxygen species mediate cyclooxygenase-2 induction during monocyte to macrophage differentiation

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AU - Barbieri, Silvia Stella

AU - Eligini, Sonia

AU - Brambilla, Marta

AU - Tremoli, Elena

AU - Colli, Susanna

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N2 - Objective: The objective of this study was to explore the relationship between monocyte differentiation into macrophages and cyclooxygenase-2 (Cox-2) expression, based upon the observation that high amounts of this enzyme, colocalizing mainly with macrophages, have been found in human atherosclerotic lesions. Moreover, the hypothesis that reactive oxygen species (ROS) could be important as mediators of Cox-2 expression during monocyte differentiation was verified. Although ROS are known as modulators of gene expression profile, their involvement in monocyte differentiation has not been explored previously. Methods: Human adherent monocytes and the promonocytic cell line U937 were differentiated into macrophages by phorbol ester (PMA). Cox-2 was evaluated in terms of protein, mRNA and activity. Intracellular ROS formation was measured by the oxidant sensitive dye 2′,7′-dichlorofluorescein diacetate. NADPH oxidase subunit p47phox was evaluated by Western blot analysis. Results: Functionally active Cox-2 is expressed during PMA-induced monocyte transition into macrophages and ROS driven by the NADPH oxidase play a critical role in this event. Conclusion: Monocyte differentiation into macrophages, possibly triggered by unquenched ROS, may contribute to the increased inflammatory response within atheromata.

AB - Objective: The objective of this study was to explore the relationship between monocyte differentiation into macrophages and cyclooxygenase-2 (Cox-2) expression, based upon the observation that high amounts of this enzyme, colocalizing mainly with macrophages, have been found in human atherosclerotic lesions. Moreover, the hypothesis that reactive oxygen species (ROS) could be important as mediators of Cox-2 expression during monocyte differentiation was verified. Although ROS are known as modulators of gene expression profile, their involvement in monocyte differentiation has not been explored previously. Methods: Human adherent monocytes and the promonocytic cell line U937 were differentiated into macrophages by phorbol ester (PMA). Cox-2 was evaluated in terms of protein, mRNA and activity. Intracellular ROS formation was measured by the oxidant sensitive dye 2′,7′-dichlorofluorescein diacetate. NADPH oxidase subunit p47phox was evaluated by Western blot analysis. Results: Functionally active Cox-2 is expressed during PMA-induced monocyte transition into macrophages and ROS driven by the NADPH oxidase play a critical role in this event. Conclusion: Monocyte differentiation into macrophages, possibly triggered by unquenched ROS, may contribute to the increased inflammatory response within atheromata.

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