1. Retinoic acid potentiates inflammatory cytokines in human mast cells: identification of mast cells as prominent constituents of the skin retinoid network.
- Author
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Babina M, Guhl S, Motakis E, Artuc M, Hazzan T, Worm M, Forrest AR, and Zuberbier T
- Subjects
- Cell Line, Cellular Microenvironment drug effects, Humans, Leukosialin metabolism, Mast Cells drug effects, Receptors, Retinoic Acid metabolism, Skin drug effects, Up-Regulation drug effects, Up-Regulation genetics, Cytokines metabolism, Inflammation Mediators metabolism, Mast Cells metabolism, Skin metabolism, Tretinoin pharmacology
- Abstract
Retinoic acid (RA), the active vitamin-A-metabolite, has well-established functions in skin homeostasis and in the immune system. Skin mast cells (MCs) combine traits of both structures, being of hematopoietic origin, but functional in the skin environment. It remains largely unknown whether mature MCs are targeted by the retinoid network. Here, we demonstrate that human skin MCs display substantial susceptibility to RA by which they are instructed to increase pro-inflammatory mediators (IL-1β, IL-8, TNF-α) but not histamine release. The effects are observed at physiological RA levels, in different microenvironments, and are largely donor-independent. RA susceptibility is owed to the cells' abundant expression of RARA, the receptor mediating MC cytokine responses. Unexpectedly, bioinformatics calculations on the FANTOM5 expression atlas revealed general enrichment of retinoid network components in MCs against other skin cells, and MCs rapidly upregulated RA responsive genes. In conclusion, MCs are important yet hitherto overlooked retinoid targets in the skin., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
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