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Attenuation of niacin‐induced prostaglandin D 2 generation by omega‐3 fatty acids in THP‐1 macrophages
Author(s) -
Siddiqui Rafat Ali,
VanHorn Justin,
Harvey Kevin A.,
Altenburg Jeffrey D.,
Xu Zhidong,
Kovacs Richard J.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.266.3
Subject(s) - niacin , docosahexaenoic acid , polyunsaturated fatty acid , eicosapentaenoic acid , chemistry , phospholipase a2 , prostaglandin , endocrinology , biochemistry , medicine , fatty acid , pharmacology , biology , enzyme
The present investigation examined the ability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), omega‐3 polyunsaturated fatty acids (PUFAs), to attenuate niacin‐induced PGs in THP‐1 macrophages. Niacin induced both PGD 2 and PGE 2 generation in a dose dependent manner. Niacin also caused an increase in cytosolic calcium and activation of cytosolic phospholipase A 2 (cPLA 2 ). The increase in PGD 2 and PGE 2 was reduced by both DHA and EPA, but not by oleic acid (OLA). Omega‐3 PUFAs efficiently incorporated into cellular phospholipids at the expense of AA, whereas OLA incorporated to a higher extent but had no effect on AA levels. Omega‐3 PUFAs also reduced surface expression of HM74A, 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 (COX‐1) activity and had no effect on Cox‐2 activity. The effects of niacin on PGD 2 generation were further confirmed using Langerhans dendritic cells. Results of the present study indicate that omega‐3 PUFAs reduced niacin‐induced PG formation by diminishing the availability of their substrate and as well as reducing the surface expression of niacin receptors. In conclusion, our study suggests that the regular use of omega‐3 PUFAs along with niacin can potentially reduce the niacin‐induced flushing response in sensitive patients.