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-Chain Gene Transcription by IL-5, IL-3, and Granulocyte-Macrophage Colony-Stimulating Factor in Human Blood Eosinophils
Allergy Department, Schering-Plough Research Institute, Kenilworth, NJ 07033
High affinity receptor for IL-5 (IL-5R), a predominant eosinophil
maturation factor, is composed of an IL-5-binding 
-chain (IL-5R)
and a signal-transducing ß-chain that is shared by IL-3 and
granulocyte-macrophage CSF (GM-CSF) receptors (IL-3R and GM-CSFR). By
Northern blot analysis of mRNAs obtained from normal human blood
eosinophils, we show in this report that the hematopoietic cytokines
IL-5, IL-3, and GM-CSF down-regulate IL-5R mRNA while up-regulating
-chain mRNAs for both IL-3R and GM-CSFR as well as the ß-chain
mRNA. More detailed characterization reveals that the down-regulation
of IL-5R mRNA is specific to IL-3, IL-5, and GM-CSF; occurs very
rapidly (reaching maximum inhibition within 2 h); is cytokine dose
dependent; and does not require protein synthesis. Nuclear run-on and
mRNA stability experiments demonstrate that cytokine-induced inhibition
of IL-5R mRNA accumulation occurs at the level of IL-5R gene
transcription, whereas enhanced accumulation of mRNAs for IL-3R and
the ß-chain results from reduced mRNA degradation. We suggest from
these experiments that in human blood eosinophils, IL-5R gene
transcription and IL-5R mRNA metabolism can be regulated by
mechanisms that are distinct from those used for IL-3R and
GM-CSFR.
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