Dexamethasone inhibits maturation, cytokine production and FcεRI expression of human cord blood-derived mast cells

S. J. Smith, A. M. Piliponsky, F. Rosenhead, U. Elchalal, A. Nagler, F. Levi-Schaffer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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 FcεRI, CD49d and c-kit was assessed by flow cytometry. Histamine release was determined by a radioenzymatic assay. Cys-LT, GM-CSF and TNF-α 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 FcεRI, CD49d and c-kit, but it inhibited the IgE-dependent enhanced expression of FcεRI. Dexamethasone (10-6 M-10-9 M) had no significant effect on FcεRI-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 FcεRI, dose-dependently inhibited the production and secretion of both GM-CSF and TNF-α. 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 FcεRI expression and mast cell production of GM-CSF and TNF-α.

Original languageAmerican English
Pages (from-to)906-913
Number of pages8
JournalClinical and Experimental Allergy
Volume32
Issue number6
DOIs
StatePublished - 2002

Keywords

  • Cys-LT
  • Glucocorticosteroids
  • Granulocyte macrophage colony stimulating factor
  • Histamine
  • Mast cells
  • Tumour necrosis factor-α

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