title: Retinoic acid inhibits in vitro development of mast cells but has no marked effect on mature human skin tryptase- and chymase-positive mast cells.
abstract: Stem cell factor plays a key role in the development of human mast cells via interaction with Kit receptor. We and other groups have previously shown that a number of cytokines can regulate the stem-cell-factor-dependent development of mast cells in vitro. In this study we investigated the effect of retinoic acid on human mast cells in vitro and in vivo. Retinoids are known to have strong modulatory effects on hematopoietic differentiation. We found that all-trans-retinoic acid, at concentrations as low as 1 nM, inhibits the stem-cell-factor-dependent differentiation of mast cells in vitro. This effect of retinoic acid was found to be on progenitor cells, whereas more mature mast cells were less affected. The use of specific agonists binding either to the RAR or the RXR nuclear receptors indicated involvement of both the RAR/RXR and RXR/RXR pathways in inhibiting mast cell differentiation. In contrast to the effects on mast cell progenitors, retinoic acid had no effect on the number of mature mast cells in skin organ cultures. Furthermore, topical treatment of normal skin with a retinoic-acid-containing cream caused an increase in the number of tryptase-positive mast cells, whereas the numbers of the major cutaneous mast cell type, tryptase- and chymase-positive mast cells, remained unaffected. Our results suggest that retinoic acid suppresses commitment of progenitor cells into the mast cell lineage and/or acts on early mast cell progenitors, whereas mature cutaneous mast cells are less susceptible to retinoic acid.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Hjertson
authors.forename: Petri K
authors.initials: PK
authors.lastname: Kivinen
authors.forename: Lina
authors.initials: L
authors.lastname: Dimberg
authors.forename: Kenneth
authors.initials: K
authors.lastname: Nilsson
authors.forename: Ilkka T
authors.initials: IT
authors.lastname: Harvima
authors.forename: Gunnar
authors.initials: G
authors.lastname: Nilsson
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002478:Cells, Cultured; D053818:Chymases; D019281:Dimerization; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009924:Organ Culture Techniques; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000378:metabolism; D047488:Retinoid X Receptors; D012697:Serine Endopeptidases / Q000032:analysis; D012867:Skin / Q000166:cytology*; D019089:Stem Cell Factor / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D053802:Tryptases; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D019089:Stem Cell Factor; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D019009:Proto-Oncogene Proteins c-kit; D012697:Serine Endopeptidases; D053818:Chymases; D053802:Tryptases