Seeing red: flushing out instigators of niacin-associated skin toxicity

摘要

The use of niacin to improve plasma lipid levels and reduce risk of myocardial infarction is limited by noxious skin effects that result from stimulation of G protein–coupled receptor 109A (GPR109A) in skin immune cells. Niacin causes vasodilation, manifest as rubor (redness) of the head and neck, providing a visible sign associated with other, more bothersome skin complaints. The working theory is that niacin provokes Langerhans cells to produce prostaglandin D_(2) (PGD_(2)), stimulating vascular DP1 receptors to cause vasodilation. In this issue of the JCI , Hanson and colleagues raise a serious challenge to this paradigm in showing that the major player in vasodilation is the keratinocyte, which produces PGE_(2), stimulating EP_(2/4) receptors, shifting the role of the Langerhans/PGD_(2)/DP_(1) pathway to that of an accomplice. They also show that the antipsoriasis drug monomethyl fumarate, itself a GPR109A agonist, provokes vasodilation through the same cells. These efforts bring us one step closer to solving a key limitation of an important cardioprotective drug and reveal that the skin response to niacin is much more complicated than previously thought.