P. Wang et al., SELECTIVE-INHIBITION OF IL-5 RECEPTOR ALPHA-CHAIN GENE-TRANSCRIPTION BY IL-5, IL-3, AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR INHUMAN BLOOD EOSINOPHILS, The Journal of immunology, 160(9), 1998, pp. 4427-4432
High affinity receptor for IL-5 (IL-SR), a predominant eosinophil matu
ration factor, is composed of an IL-5-binding or-chain (IL-5R alpha) a
nd a signal-transducing beta-chain that is shared by IL-3 and granuloc
yte-macrophage CSF (GM-CSF) receptors (IL-SR 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, an
d GM-CSF down-regulate IL-5R alpha mRNA while up-regulating alpha-chai
n mRNAs for both IL-3R and GM-CSFR as well as the beta-chain mRNA, Mor
e detailed characterization reveals that the down-regulation of IL-5R
alpha 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 stabil
ity experiments demonstrate that cytokine-induced inhibition of IL-5R
alpha mRNA accumulation occurs at the level of IL-5R alpha gene transc
ription, whereas enhanced accumulation of mRNAs for IL-3R alpha and th
e beta-chain results from reduced mRNA degradation. We suggest from th
ese experiments that in human blood eosinophils, IL-5R alpha gene tran
scription and IL-5R alpha mRNA metabolism can be regulated by mechanis
ms that are distinct from those used for IL-3R alpha and GM-CSFR alpha
.