title: Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells.
abstract: The antidyslipidemic drug nicotinic acid (niacin) has been used for decades. One of the major problems of the therapeutical use of nicotinic acid is a strong cutaneous vasodilation called flushing, which develops in almost every patient taking nicotinic acid. Nicotinic acid-induced flushing has been shown to be mediated by the nicotinic acid receptor GPR109A and to involve the formation of vasodilatory prostanoids. However, the cellular mechanisms underlying this short-term effect are unknown. Here, we show that epidermal Langerhans cells are essential for the cutaneous flushing response induced by nicotinic acid. Langerhans cells respond with an increase in [Ca(2+)](i) to nicotinic acid and express prostanoid synthases required for the formation of the vasodilatory prostanoids prostaglandin E(2) and prostaglandin D(2). Depletion of epidermal Langerhans cells but not of macrophages or dendritic cells abrogates nicotinic acid-induced flushing. These data unexpectedly identify epidermal Langerhans cells as essential mediators of nicotinic acid-induced flushing and may help to generate new strategies to suppress the unwanted effects of nicotinic acid. In addition, our results suggest that Langerhans cells besides their immunological roles are also involved in the local regulation of dermal blood flow.
authors.affiliation: Institute of Pharmacology, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Benyó
authors.forename: Andreas
authors.initials: A
authors.lastname: Gille
authors.forename: Clare L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Björn E
authors.initials: BE
authors.lastname: Clausen
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
mesh_terms: D000818:Animals; D002469:Cell Separation; D005434:Flow Cytometry; D005453:Fluorescence; D005483:Flushing / Q000139:chemically induced*; D007801:Langerhans Cells / Q000187:drug effects*; D051379:Mice; D009525:Niacin / Q000009:adverse effects*; D012867:Skin / Q000166:cytology / Q000187:drug effects*
chemical_list: D009525:Niacin