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 [Ca2+]i to nicotinic acid and express prostanoid synthases required for the formation of the vasodilatory prostanoids prostaglandin E2 and prostaglandin D2. 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.
Footnotes
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This study was supported by Hungarian OTKA (K62375) and the Deutsche Forschungsgemeinschaft. Z.B. was supported by a Marie Curie Individual Fellowship. A.G. was supported by a long-term European Molecular Biology Oraganization fellowship.
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Z.B. and A.G. contributed equally to this work.
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ABBREVIATIONS: HDL, high density lipoprotein; DT, diphtheria toxin; DTR, diphtheria toxin receptor; LDF, laser-Doppler flow; PGE2, prostaglandin E2; PGD2, prostaglandin D2; mPGES-1 and mPGES-2, type 1 and type 2 PGE2 synthases; MHC, major histocompatibility complex; PE, phosphatidylethanolamine; GFP, green fluorescent protein; FITC, fluorescein isothiocyanate; PBS, phosphate-buffered saline.
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↵1 Current affiliation: Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
- Received September 12, 2006.
- Accepted September 28, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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