Dexamethasone and FK506 inhibit expression of distinct subsets of chemokines in human mast cells

Atsushi Kato, Regina T. Chustz, Takahisa Ogasawara, Marianna Kulka, Hirohisa Saito, Robert P. Schleimerand, Kenji Matsumoto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Mast cells produce a large amount of several chemokines after cross-linking of FcεRI and participate in the pathogenesis of allergic diseases. The objective of this study was to comprehensively investigate FcεRI-mediated chemokine induction in human mast cells and the effect of a corticosteroid (dexamethasone) and a calcineurin inhibitor (FK506). Human peripheral blood-derived mast cells were stimulated with anti-IgE Ab in the presence of dexamethasone or FK506. Gene expression profiles were evaluated using GeneChip and confirmed by real-time PCR, and chemokine concentrations were measured by cytometric bead arrays and ELISA. Expression of eight chemokines was significantly induced in mast cells by anti-IgE stimulation. Induction of CCL2, CCL7, CXCL3, and CXCL8 by anti-IgE was significantly inhibited by dexamethasone but was enhanced by FK506. In contrast, induction of CCL1, CCL3, CCL4, and CCL18 was significantly inhibited by FK506 but, with the exception of CCL1, was enhanced by dexamethasone. Combination of dexamethasone and FK506 suppressed production of all chemokines by anti-IgE stimulation. Studies using protease inhibitors indicate that mast cell proteases may degrade several of the chemokines. These results suggest that corticosteroids and calcineurin inhibitors inhibit expression of distinct subsets of chemokines, and a combination of these drugs almost completely suppresses the induction of all chemokine genes in human mast cells in response to FcεRI-dependent stimulation. This implies that a combination of a corticosteroid and a calcineurin inhibitor may be more effective than each single agent for the treatment of allergic diseases in which mast cell-derived chemokines play a major role.

Original languageEnglish (US)
Pages (from-to)7233-7243
Number of pages11
JournalJournal of Immunology
Volume182
Issue number11
DOIs
StatePublished - Jun 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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