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Two distinct pathways of interleukin-5 synthesis in allergen-specific human
T-cell clones are suppressed by glucocorticoids
A Mori, O Kaminuma, M Suko, S Inoue, T Ohmura, A Hoshino, Y Asakura, K Miyazawa, T Yokota, Y Okumura, K Ito and H Okudaira
Department of Medicine, Faculty of Medicine, University of Tokyo,
Bunkyo-ku, Japan.
Glucocorticoids (GC) have long been used as the most effective agents for
the treatment of allergic diseases accompanied by eosinophilia such as
chronic asthma and atopic dermatitis. The development of chronic
eosinophilic inflammation is dependent on interleukin-5 (IL-5), a selective
eosinophil-activating factor, produced by helper T cells. To delineate the
regulatory mechanisms of human IL-5 synthesis, we established
allergen-specific CD4+ T-cell clones from asthmatic patients. GC
efficiently suppressed IL-5 synthesis of T-cell clones activated via either
T-cell receptor (TCR) or IL-2 receptor (IL-2R). Induction of IL-5 mRNA upon
TCR and IL-2R stimulation was totally inhibited by dexamethasone. Human
IL-5 promoter/enhancer-luciferase gene construct transfected to T-cell
clones was transcribed on either TCR or IL-2R stimulation and was clearly
downregulated by dexamethasone, indicating that the approximately 500-bp
human IL-5 gene segment located 5' upstream of the coding region contains
activation- inducible enhancer elements responsible for the regulation by
GC. Electrophoretic mobility shift assay analysis suggested that AP-1 and
NF-kappaB are among the possible targets of GC actions on TCR- stimulated T
cells. NF-AT and NF-kappaB were not significantly induced by IL-2
stimulation. Our results showing that GC suppressed IL-5 production by
human CD4+ T cells activated by two distinct stimuli, TCR and IL-2R
stimulation, underscore the efficacy of GC in the treatment of allergic
diseases via suppression of T-cell IL-5 synthesis.
Volume 89,
Issue 8,
pp. 2891-2900,
04/15/1997
Copyright © 1997 by The American Society of Hematology
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