Attenuation of niacin-induced prostaglandin D(2) generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells

Abstract

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 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). The increase in PGD(2) and PGE(2) 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 PGD(2) 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.