Reciprocal regulation of cultured human mast cell cytokine production by IL-4 and IFN-γ

Hiroshi Tachimoto, Motohiro Ebisawa*, Tomohide Hasegawa, Tomoko Kashiwabara, Chisei Ra, Bruce S. Bochner, Katsushi Miura, Hirohisa Saito

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background: T(H)1 and T(H)2 cytokines are thought to regulate allergic inflammation. Objective: Two key regulatory cytokines, IL-4 and IFN-γ, were examined for their effects on cytokine production by cultured human mast cells (CHMCs). Methods: CHMCs were obtained by culturing cord blood-derived CD34 + cells in the presence of stem cell factor and IL-6 for 14 to 16 weeks. CHMCs were passively sensitized with human myeloma IgE and supplemented with or without IL-4 or IFN-γ. After the sensitization, CHMCs were stimulated with anti-FcεRIα mAb. Concentrations of secreted cytokines were measured by using ELISA, and cytokine messenger RNA was analyzed by using quantitative competitive RT-PCR. Results: IL-4 profoundly enhanced FcεRI-mediated production of macrophage inflammatory protein (MIP) 1α IL-8, and GM-CSF. For example, the enhancement by IL-4 (10 ng/Ml) of the production of MIP-1α IL- 8, and GM-CSF was 25-, 7-, and 90-fold, respectively, after 6 hours. IL-4 also enhanced levels of FcεRI-induced cytokine messenger RNA but to a lesser degree. In contrast, IFN-γ inhibited FcεRI-induced production of MIP-1α, IL-8, and GM-CSF. For example, the inhibition by IFN-γ (10 ng/mL) of FcεRI- mediated production of MIP-1α, IL-8, and GM-CSF was 80%, 75%, and 95%, respectively. IFN-γ also suppressed FcεRI-induced messenger RNA expression of these cytokines. Neither IL-4 nor IFN-γ affected the kinetics of cytokine production by CHMCs. Conclusion: These data suggest that IL-4 and IFN-γ may influence allergic reactions by modulating human mast cell cytokine production.

Original languageEnglish (US)
Pages (from-to)141-149
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume106
Issue number1 I
DOIs
StatePublished - Jan 1 2000

Keywords

  • Allergy
  • Cellular activation
  • Chemokines
  • Cytokines
  • Human
  • IgE
  • Mast cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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