Attenuation of niacin-induced prostaglandin D2 generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells

Justin VanHorn1, Jeffrey D Altenburg1, Kevin A Harvey1, Zhidong Xu1, Richard J Kovacs2, Rafat A Siddiqui1,31Cellular Biochemistry Laboratory, Methodist Research Institute, Indianapolis, 2Krannert Institute of Cardiology, Indianapolis, 3Department of Medicine, Indiana University School of Medicine, I...

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Autores principales:	VanHorn J, Altenburg JD, Harvey KA, Xu Z, Kovacs RJ, Siddiqui RA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/bbc1d11110d64cb88a36ad7e6e678bbf
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spelling	oai:doaj.org-article:bbc1d11110d64cb88a36ad7e6e678bbf2021-12-02T11:16:21ZAttenuation of niacin-induced prostaglandin D2 generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells1178-7031https://doaj.org/article/bbc1d11110d64cb88a36ad7e6e678bbf2012-03-01T00:00:00Zhttp://www.dovepress.com/attenuation-of-niacin-induced-prostaglandin-d2-generation-by-omega-3-f-a9481https://doaj.org/toc/1178-7031Justin VanHorn1, Jeffrey D Altenburg1, Kevin A Harvey1, Zhidong Xu1, Richard J Kovacs2, Rafat A Siddiqui1,31Cellular Biochemistry Laboratory, Methodist Research Institute, Indianapolis, 2Krannert Institute of Cardiology, Indianapolis, 3Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USAAbstract: Niacin, also known as nicotinic acid, is an organic compound that has several cardio-beneficial effects. However, its use is limited due to the induction of a variable flushing response in most individuals. Flushing occurs from a niacin receptor mediated generation of prostaglandins from arachidonic acid metabolism. This study examined the ability of docosahexaenoic acid, eicosapentaenoic acid, and omega-3 polyunsaturated fatty acids (PUFAs), to attenuate niacin-induced prostaglandins in THP-1 macrophages. Niacin induced both PGD2 and PGE2 generation in a dose-dependent manner. Niacin also caused an increase in cytosolic calcium and activation of cytosolic phospholipase A2. The increase in PGD2 and PGE2 was reduced by both docosahexaenoic acid and eicosapentaenoic acid, but not by oleic acid. Omega-3 PUFAs efficiently incorporated into cellular phospholipids at the expense of arachidonic acid, whereas oleic acid incorporated to a higher extent but had no effect on arachidonic acid levels. Omega-3 PUFAs also reduced surface expression of GPR109A, a human niacin receptor. Furthermore, omega-3 PUFAs also inhibited the niacin-induced increase in cytosolic calcium. Niacin and/or omega-3 PUFAs minimally affected cyclooxygenase-1 activity and had no effect on cyclooxygenase -2 activity. The effects of niacin on PGD2 generation were further confirmed using Langerhans dendritic cells. Results of the present study indicate that omega-3 PUFAs reduced niacin-induced prostaglandins formation by diminishing the availability of their substrate, as well as reducing the surface expression of niacin receptors. In conclusion, this study suggests that the regular use of omega-3 PUFAs along with niacin can potentially reduce the niacin-induced flushing response in sensitive patients.Keywords: flushing, prostaglandin E2, phospholipids, GPR109A, cardiovascular, docosahexaenoic acid, arachidonic acidVanHorn JAltenburg JDHarvey KAXu ZKovacs RJSiddiqui RADove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2012, Iss default, Pp 37-50 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	Pathology RB1-214 Therapeutics. Pharmacology RM1-950 VanHorn J Altenburg JD Harvey KA Xu Z Kovacs RJ Siddiqui RA Attenuation of niacin-induced prostaglandin D2 generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells
description	Justin VanHorn1, Jeffrey D Altenburg1, Kevin A Harvey1, Zhidong Xu1, Richard J Kovacs2, Rafat A Siddiqui1,31Cellular Biochemistry Laboratory, Methodist Research Institute, Indianapolis, 2Krannert Institute of Cardiology, Indianapolis, 3Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USAAbstract: Niacin, also known as nicotinic acid, is an organic compound that has several cardio-beneficial effects. However, its use is limited due to the induction of a variable flushing response in most individuals. Flushing occurs from a niacin receptor mediated generation of prostaglandins from arachidonic acid metabolism. This study examined the ability of docosahexaenoic acid, eicosapentaenoic acid, and omega-3 polyunsaturated fatty acids (PUFAs), to attenuate niacin-induced prostaglandins in THP-1 macrophages. Niacin induced both PGD2 and PGE2 generation in a dose-dependent manner. Niacin also caused an increase in cytosolic calcium and activation of cytosolic phospholipase A2. The increase in PGD2 and PGE2 was reduced by both docosahexaenoic acid and eicosapentaenoic acid, but not by oleic acid. Omega-3 PUFAs efficiently incorporated into cellular phospholipids at the expense of arachidonic acid, whereas oleic acid incorporated to a higher extent but had no effect on arachidonic acid levels. Omega-3 PUFAs also reduced surface expression of GPR109A, a human niacin receptor. Furthermore, omega-3 PUFAs also inhibited the niacin-induced increase in cytosolic calcium. Niacin and/or omega-3 PUFAs minimally affected cyclooxygenase-1 activity and had no effect on cyclooxygenase -2 activity. The effects of niacin on PGD2 generation were further confirmed using Langerhans dendritic cells. Results of the present study indicate that omega-3 PUFAs reduced niacin-induced prostaglandins formation by diminishing the availability of their substrate, as well as reducing the surface expression of niacin receptors. In conclusion, this study suggests that the regular use of omega-3 PUFAs along with niacin can potentially reduce the niacin-induced flushing response in sensitive patients.Keywords: flushing, prostaglandin E2, phospholipids, GPR109A, cardiovascular, docosahexaenoic acid, arachidonic acid
format	article
author	VanHorn J Altenburg JD Harvey KA Xu Z Kovacs RJ Siddiqui RA
author_facet	VanHorn J Altenburg JD Harvey KA Xu Z Kovacs RJ Siddiqui RA
author_sort	VanHorn J
title	Attenuation of niacin-induced prostaglandin D2 generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells
title_short	Attenuation of niacin-induced prostaglandin D2 generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells
title_full	Attenuation of niacin-induced prostaglandin D2 generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells
title_fullStr	Attenuation of niacin-induced prostaglandin D2 generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells
title_full_unstemmed	Attenuation of niacin-induced prostaglandin D2 generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells
title_sort	attenuation of niacin-induced prostaglandin d2 generation by omega-3 fatty acids in thp-1 macrophages and langerhans dendritic cells
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/bbc1d11110d64cb88a36ad7e6e678bbf
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Attenuation of niacin-induced prostaglandin D2 generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells

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