Quantification of indoleamine 2,3-dioxygenase gene induction in atopic and non-atopic monocytes after ligation of the high-affinity receptor for IgE, Fc(epsilon)RI and interferon-gamma stimulation.
Antigen-presenting cells (APCs) are crucial in regulating the outcome of T cell responses. Certain APCs are able to down-regulate T cell proliferation in vitro by inducing the enzyme indoleamine 2,3-dioxygenase (IDO) upon interferon-gamma (IFN-gamma) stimulation. IDO is the rate-limiting enzyme in the catabolism of the essential amino acid tryptophan. A lack of extracellular tryptophan creates environments in which cells become starved for this amino acid. The high-affinity receptor for IgE, Fc(epsilon)RI, is the principal receptor for the binding of specific IgE in type I-mediated allergies. We demonstrated recently that IDO is overexpressed in Fc(epsilon)RI-stimulated monocytes. In the present study, we performed quantification of IDO gene induction after treatment of atopic (Fc(epsilon)RI(high)) and non-atopic (Fc(epsilon)RI(low/-)) monocytes with IgE/anti-IgE and IFN-gamma. By quantitative PCR ELISA, we found IDO molecule induction in atopic monocytes was enhanced about 50-fold over non-atopic monocytes after ligation of Fc(epsilon)RI. Stimulation with IFN-gamma at a concentration of 100 U/ml in culture medium caused an increase in IDO gene copy numbers in atopics of about fourfold over that of non-atopics. This comparative quantification study demonstrates clearly the regulation of IDO gene expression by Fc(epsilon)RI and discloses differences thereof in atopic and non-atopic cells upon inflammatory stimuli.
von Bubnoff
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Department of Dermatology, Friedrich-Wilhelms-University, Bonn, Germany. d.bubnoff@uni-bonn.de
Bezold
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Matz
H
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Hanau
D
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De La Salle
H
H
Bieber
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T
D000938:Antigen-Presenting Cells / Q000276:immunology*; D016022:Case-Control Studies; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D017455:Receptors, IgE / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology*; D014366:Tryptophan Oxygenase / Q000032:analysis / Q000235:genetics*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D017455:Receptors, IgE; D007073:Immunoglobulin E; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase