Langerhans Cells Release Prostaglandin D2 in Response to Nicotinic Acid
| Autor: | Yaron Hakak, Ibragim Gaidarov, Dominic P. Behan, Jeremy G. Richman, Dominique Maciejewski-Lenoir, Daniel T. Connolly |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Langerhans cell Prostaglandin Dermatology In Vitro Techniques Receptors Nicotinic Isonicotinic acid Niacin Biochemistry Receptors G-Protein-Coupled Mice chemistry.chemical_compound Internal medicine Flushing medicine Animals Humans Tissue Distribution RNA Messenger Antigen-presenting cell Molecular Biology Cells Cultured Hypolipidemic Agents Oligonucleotide Array Sequence Analysis Skin integumentary system Prostaglandin D2 Cell Biology Molecular biology Mice Inbred C57BL B vitamins Endocrinology medicine.anatomical_structure Nicotinic agonist chemistry Cell culture Langerhans Cells lipids (amino acids peptides and proteins) |
| Zdroj: | Journal of Investigative Dermatology. 126:2637-2646 |
| ISSN: | 0022-202X |
| Popis: | Nicotinic acid, used for atherosclerosis treatment, has an adverse effect of skin flushing. The flushing mechanism, thought to be caused by the release of prostaglandin D(2) (PGD(2)), is not well understood. We aimed to identify which cells mediate the flushing effect. Nicotinic acid receptor (GPR109A) gene expression was assessed in various tissues and cell lines. Cells expressing GPR109A mRNA were further assayed for PGD(2) release in response to nicotinic acid. Of all samples, only skin was able to release PGD(2) upon stimulation with nicotinic acid. The responsive cells were localized to the epidermis, and immunocytochemical studies revealed the presence of GPR109A on epidermal Langerhans cells. CD34+ cells isolated from human blood and differentiated into Langerhans cells (hLC-L) also showed GPR109A expression. IFNgamma treatment increased both mRNA and plasma membrane expression of GPR109A. IFNgamma-stimulated hLC-Ls released PGD(2) in response to nicotinic acid in a dose-dependant manner (effector concentration for half-maximum response=1.2 mM+/-0.7). Acifran, a structurally distinct GPR109A ligand, also increased PGD(2) release, whereas isonicotinic acid, a nicotinic acid analog with low affinity for GPR109A, had no effect. These results suggest that nicotinic acid mediates its flushing side effect by interacting with GPR109A on skin Langerhans cells, resulting in release of PGD(2). |
| Databáze: | OpenAIRE |
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