PMID- 31540502 OWN - NLM STAT- MEDLINE DCOM- 20200325 LR - 20200325 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 11 IP - 9 DP - 2019 Sep 18 TI - N-Eicosapentaenoyl Dopamine, A Conjugate of Dopamine and Eicosapentaenoic Acid (EPA), Exerts Anti-inflammatory Properties in Mouse and Human Macrophages. LID - 10.3390/nu11092247 [doi] LID - 2247 AB - 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-3alpha (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-1beta (IL-1beta) 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. FAU - Augimeri, Giuseppina AU - Augimeri G AD - Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. giusy.augimeri@gmail.com. FAU - Plastina, Pierluigi AU - Plastina P AUID- ORCID: 0000-0002-8534-4130 AD - Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. FAU - Gionfriddo, Giulia AU - Gionfriddo G AD - Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. giu.gionfriddo@gmail.com. FAU - Rovito, Daniela AU - Rovito D AD - Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. rovitod@igbmc.fr. FAU - Giordano, Cinzia AU - Giordano C AD - Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. cinzia.giordano@unical.it. FAU - Fazio, Alessia AU - Fazio A AD - Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. alessia.fazio@unical.it. FAU - Barone, Ines AU - Barone I AD - Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. ines.barone@unical.it. FAU - Catalano, Stefania AU - Catalano S AD - Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. stefania.catalano@unical.it. FAU - Ando, Sebastiano AU - Ando S AD - Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. sebastiano.ando@unical.it. FAU - Bonofiglio, Daniela AU - Bonofiglio D AUID- ORCID: 0000-0002-4142-0496 AD - Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. daniela.bonofiglio@unical.it. FAU - Meijerink, Jocelijn AU - Meijerink J AD - Division of Human Nutrition and Health, Wageningen University, 6700 AA Wageningen, The Netherlands. jocelijn.meijerink@wur.nl. FAU - Witkamp, Renger AU - Witkamp R AUID- ORCID: 0000-0002-7935-8261 AD - Division of Human Nutrition and Health, Wageningen University, 6700 AA Wageningen, The Netherlands. renger.witkamp@wur.nl. LA - eng PT - Journal Article DEP - 20190918 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Fatty Acids, Unsaturated) RN - AAN7QOV9EA (Eicosapentaenoic Acid) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Anti-Inflammatory Agents/chemistry/*pharmacology MH - Cells, Cultured MH - Cyclooxygenase 2/metabolism MH - Cytokines/metabolism MH - Dopamine/chemistry/*pharmacology MH - Eicosapentaenoic Acid/analogs & derivatives/chemistry/*pharmacology MH - Fatty Acids, Unsaturated/metabolism MH - Humans MH - Macrophages/*drug effects/metabolism MH - Mice MH - RAW 264.7 Cells PMC - PMC6769480 OTO - NOTNLM OT - N-acyl dopamine OT - N-eicosapentaenoyl dopamine OT - cyclooxygenase-2 OT - cytokines OT - endocannabinoid OT - inflammation OT - polyunsaturated fatty acids (PUFAs) COIS- The authors declare no conflict of interest. EDAT- 2019/09/22 06:00 MHDA- 2020/03/26 06:00 PMCR- 2019/09/01 CRDT- 2019/09/22 06:00 PHST- 2019/07/23 00:00 [received] PHST- 2019/09/04 00:00 [revised] PHST- 2019/09/16 00:00 [accepted] PHST- 2019/09/22 06:00 [entrez] PHST- 2019/09/22 06:00 [pubmed] PHST- 2020/03/26 06:00 [medline] PHST- 2019/09/01 00:00 [pmc-release] AID - nu11092247 [pii] AID - nutrients-11-02247 [pii] AID - 10.3390/nu11092247 [doi] PST - epublish SO - Nutrients. 2019 Sep 18;11(9):2247. doi: 10.3390/nu11092247.