Dexamethasone inhibits maturation, cytokine production and Fc epsilon RI expression of human cord blood-derived mast cells.
BACKGROUND
Mast cells are responsible for eliciting the early phase and for contributing to the development of the late phase of allergic reactions, through the release of cytokines and other inflammatory mediators.


OBJECTIVE
To assess whether the glucocorticoid dexamethasone has a direct effect on mast cell progenitor maturation and on mature cord blood-derived mast cell properties.


METHODS
Mast cells were obtained by culturing human umbilical cord blood mononuclear cells with stem cell factor, IL-6 and prostaglandin E2. Mast cell numbers were assessed by Toluidine Blue staining and immunocytochemistry of tryptase positive cells. The expression of Fc epsilon RI, CD49d and c-kit was assessed by flow cytometry. Histamine release was determined by a radioenzymatic assay. Cys-LT, GM-CSF and TNF-alpha production and release were determined by ELISA.


RESULTS
Dexamethasone (10(-6) M-10(-9) M) time- and dose-dependently inhibited the maturation of the mast cell progenitors. Dexamethasone did not affect the basal expression of Fc epsilon RI, CD49d and c-kit, but it inhibited the IgE-dependent enhanced expression of Fc epsilon RI. Dexamethasone (10(-6) M-10(-9) M) had no significant effect on Fc epsilon RI-dependent histamine release or the synthesis and release of Cys-LT from the mature mast cells. However, pre-incubation of the mast cell cultures with dexamethasone for 1 h, prior to cross-linking of Fc epsilon RI, dose-dependently inhibited the production and secretion of both GM-CSF and TNF-alpha.


CONCLUSIONS
From these in vitro data we propose that glucocorticosteroids are effective drugs in the management of allergic inflammation due to their capacity to inhibit mast cell development, IgE-dependent Fc epsilon RI expression and mast cell production of GM-CSF and TNF-alpha.
Smith
S J
SJ
Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Hadassah University Hospital of The Hebrew University, Jerusalem, Israel.
Piliponsky
A M
AM
Rosenhead
F
F
Elchalal
U
U
Nagler
A
A
Levi-Schaffer
F
F
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism*; D005938:Glucocorticoids; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology; D039441:Integrin alpha4 / Q000096:biosynthesis / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology*; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D017455:Receptors, IgE; D039441:Integrin alpha4; D007073:Immunoglobulin E; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor