N-Eicosapentaenoyl Dopamine, A Conjugate of Dopamine and Eicosapentaenoic Acid (EPA), Exerts Anti-inflammatory Properties in Mouse and Human Macrophages

Giuseppina Augimeri, Pierluigi Plastina, Giulia Gionfriddo, Daniela Rovito, Cinzia Giordano, Alessia Fazio, Ines Barone, Stefania Catalano, Sebastiano Andò, Daniela Bonofiglio, Jocelijn Meijerink, Renger Witkamp

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

A large body of evidence suggests that dietary n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), contribute to a reduced inflammatory tone thereby lowering the risk for several chronic and degenerative diseases. Different mechanisms have been proposed to explain these anti-inflammatory effects, including those involving endocannabinoids and endocannabinoid-like molecules. In this context, fatty acid amides (FAAs), conjugates of fatty acids with amines or amino acids, are an emerging class of compounds. Dopamine conjugates of DHA (N-docosahexaenoyl dopamine, DHDA) and EPA (N-eicosapentaenoyl dopamine, EPDA) have previously been shown to induce autophagy, apoptosis, and cell death in different tumor lines. Additionally, DHDA has displayed anti-inflammatory properties in vitro. Here, we tested the immune-modulatory properties of EPDA in mouse RAW 264.7 and human THP-1 macrophages stimulated with lipopolysaccharide (LPS). EPDA suppressed the production of monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in both cell lines, and nitric oxide (NO), and macrophage-inflammatory protein-3α (MIP3A) in RAW 264.7 macrophages. At a transcriptional level, EPDA attenuated cyclooxygenase-2 (COX-2) expression in both cell lines and that of MCP-1, IL-6, and interleukin-1β (IL-1β) in THP-1 macrophages. Although further research is needed to reveal whether EPDA is an endogenous metabolite, our data suggest that this EPA-derived conjugate possesses interesting immune-modulating properties.

Original languageEnglish
Article number2247
JournalNutrients
Volume11
Issue number9
DOIs
Publication statusPublished - 18 Sep 2019

Fingerprint

Eicosapentaenoic Acid
eicosapentaenoic acid
dopamine
anti-inflammatory activity
Dopamine
macrophages
Anti-Inflammatory Agents
Macrophages
mice
Endocannabinoids
Docosahexaenoic Acids
Chemokine CCL2
Interleukin-6
Fatty Acids
docosahexaenoic acid
interleukin-6
Macrophage Inflammatory Proteins
Cell Line
cell lines
Autophagy

Keywords

  • cyclooxygenase-2
  • cytokines
  • endocannabinoid
  • inflammation
  • N-acyl dopamine
  • N-eicosapentaenoyl dopamine
  • polyunsaturated fatty acids (PUFAs)

Cite this

Augimeri, Giuseppina ; Plastina, Pierluigi ; Gionfriddo, Giulia ; Rovito, Daniela ; Giordano, Cinzia ; Fazio, Alessia ; Barone, Ines ; Catalano, Stefania ; Andò, Sebastiano ; Bonofiglio, Daniela ; Meijerink, Jocelijn ; Witkamp, Renger. / N-Eicosapentaenoyl Dopamine, A Conjugate of Dopamine and Eicosapentaenoic Acid (EPA), Exerts Anti-inflammatory Properties in Mouse and Human Macrophages. In: Nutrients. 2019 ; Vol. 11, No. 9.
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abstract = "A large body of evidence suggests that dietary n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), contribute to a reduced inflammatory tone thereby lowering the risk for several chronic and degenerative diseases. Different mechanisms have been proposed to explain these anti-inflammatory effects, including those involving endocannabinoids and endocannabinoid-like molecules. In this context, fatty acid amides (FAAs), conjugates of fatty acids with amines or amino acids, are an emerging class of compounds. Dopamine conjugates of DHA (N-docosahexaenoyl dopamine, DHDA) and EPA (N-eicosapentaenoyl dopamine, EPDA) have previously been shown to induce autophagy, apoptosis, and cell death in different tumor lines. Additionally, DHDA has displayed anti-inflammatory properties in vitro. Here, we tested the immune-modulatory properties of EPDA in mouse RAW 264.7 and human THP-1 macrophages stimulated with lipopolysaccharide (LPS). EPDA suppressed the production of monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in both cell lines, and nitric oxide (NO), and macrophage-inflammatory protein-3α (MIP3A) in RAW 264.7 macrophages. At a transcriptional level, EPDA attenuated cyclooxygenase-2 (COX-2) expression in both cell lines and that of MCP-1, IL-6, and interleukin-1β (IL-1β) in THP-1 macrophages. Although further research is needed to reveal whether EPDA is an endogenous metabolite, our data suggest that this EPA-derived conjugate possesses interesting immune-modulating properties.",
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author = "Giuseppina Augimeri and Pierluigi Plastina and Giulia Gionfriddo and Daniela Rovito and Cinzia Giordano and Alessia Fazio and Ines Barone and Stefania Catalano and Sebastiano And{\`o} and Daniela Bonofiglio and Jocelijn Meijerink and Renger Witkamp",
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Augimeri, G, Plastina, P, Gionfriddo, G, Rovito, D, Giordano, C, Fazio, A, Barone, I, Catalano, S, Andò, S, Bonofiglio, D, Meijerink, J & Witkamp, R 2019, 'N-Eicosapentaenoyl Dopamine, A Conjugate of Dopamine and Eicosapentaenoic Acid (EPA), Exerts Anti-inflammatory Properties in Mouse and Human Macrophages' Nutrients, vol. 11, no. 9, 2247. https://doi.org/10.3390/nu11092247

N-Eicosapentaenoyl Dopamine, A Conjugate of Dopamine and Eicosapentaenoic Acid (EPA), Exerts Anti-inflammatory Properties in Mouse and Human Macrophages. / Augimeri, Giuseppina; Plastina, Pierluigi; Gionfriddo, Giulia; Rovito, Daniela; Giordano, Cinzia; Fazio, Alessia; Barone, Ines; Catalano, Stefania; Andò, Sebastiano; Bonofiglio, Daniela; Meijerink, Jocelijn; Witkamp, Renger.

In: Nutrients, Vol. 11, No. 9, 2247, 18.09.2019.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - N-Eicosapentaenoyl Dopamine, A Conjugate of Dopamine and Eicosapentaenoic Acid (EPA), Exerts Anti-inflammatory Properties in Mouse and Human Macrophages

AU - Augimeri, Giuseppina

AU - Plastina, Pierluigi

AU - Gionfriddo, Giulia

AU - Rovito, Daniela

AU - Giordano, Cinzia

AU - Fazio, Alessia

AU - Barone, Ines

AU - Catalano, Stefania

AU - Andò, Sebastiano

AU - Bonofiglio, Daniela

AU - Meijerink, Jocelijn

AU - Witkamp, Renger

PY - 2019/9/18

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N2 - A large body of evidence suggests that dietary n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), contribute to a reduced inflammatory tone thereby lowering the risk for several chronic and degenerative diseases. Different mechanisms have been proposed to explain these anti-inflammatory effects, including those involving endocannabinoids and endocannabinoid-like molecules. In this context, fatty acid amides (FAAs), conjugates of fatty acids with amines or amino acids, are an emerging class of compounds. Dopamine conjugates of DHA (N-docosahexaenoyl dopamine, DHDA) and EPA (N-eicosapentaenoyl dopamine, EPDA) have previously been shown to induce autophagy, apoptosis, and cell death in different tumor lines. Additionally, DHDA has displayed anti-inflammatory properties in vitro. Here, we tested the immune-modulatory properties of EPDA in mouse RAW 264.7 and human THP-1 macrophages stimulated with lipopolysaccharide (LPS). EPDA suppressed the production of monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in both cell lines, and nitric oxide (NO), and macrophage-inflammatory protein-3α (MIP3A) in RAW 264.7 macrophages. At a transcriptional level, EPDA attenuated cyclooxygenase-2 (COX-2) expression in both cell lines and that of MCP-1, IL-6, and interleukin-1β (IL-1β) in THP-1 macrophages. Although further research is needed to reveal whether EPDA is an endogenous metabolite, our data suggest that this EPA-derived conjugate possesses interesting immune-modulating properties.

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KW - cyclooxygenase-2

KW - cytokines

KW - endocannabinoid

KW - inflammation

KW - N-acyl dopamine

KW - N-eicosapentaenoyl dopamine

KW - polyunsaturated fatty acids (PUFAs)

U2 - 10.3390/nu11092247

DO - 10.3390/nu11092247

M3 - Article

VL - 11

JO - Nutrients

JF - Nutrients

SN - 2072-6643

IS - 9

M1 - 2247

ER -