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Retinoic Acid Negatively Impacts Proliferation and MCTC Specific Attributes of Human Skin Derived Mast Cells, but Reinforces Allergic Stimulability.
- Source :
- International Journal of Molecular Sciences; Mar2017, Vol. 18 Issue 3, p525, 15p, 4 Graphs
- Publication Year :
- 2017
-
Abstract
- The Vitamin-A-metabolite retinoic acid (RA) acts as a master regulator of cellular programs. Mast cells (MCs) are primary effector cells of type-I-allergic reactions. We recently uncovered that human cutaneous MCs are enriched with RA network components over other skin cells. Yet, direct experimental evidence on the significance of the RA-MC axis is limited. Here, skin-derived cultured MCs were exposed to RA for seven days and investigated by flow-cytometry (BrdU incorporation, Annexin/PI, Fc"RI), microscopy, RT-qPCR, histamine quantitation, protease activity, and degranulation assays. We found that whileMCsize and granularity remained unchanged, RA potently interfered with MC proliferation. Conversely, a modest survival-promoting effect from RA was noted. The granule constituents, histamine and tryptase, remained unaffected, while RA had a striking impact on MC chymase, whose expression dropped by gene and by peptidase activity. The newly uncovered MRGPRX2 performed similarly to chymase. Intriguingly, RA fostered allergic MC degranulation, in a way completely uncoupled from Fc"RI expression, but it simultaneously restricted MRGPRX2-triggered histamine release in agreement with the reduced receptor expression. Vitamin-A-derived hormones thus re-shape skin-derived MCs numerically, phenotypically, and functionally. A general theme emerges, implying RA to skew MCs towards processes associated with (allergic) inflammation, while driving them away from the skin-imprinted MC<subscript>TC</subscript> ("MCs containing tryptase and chymase") signature (chymase, MRGPRX2). Collectively, MCs are substantial targets of the skin retinoid network. [ABSTRACT FROM AUTHOR]
- Subjects :
- TRETINOIN
CELL proliferation
MAST cells
CELL cycle
TRYPTASE
CHYMASES
Subjects
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 18
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 122244029
- Full Text :
- https://doi.org/10.3390/ijms18030525