Selective inhibition of IL-5 receptor alpha-chain gene transcription by IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor in human blood eosinophils.
High affinity receptor for IL-5 (IL-5R), a predominant eosinophil maturation factor, is composed of an IL-5-binding alpha-chain (IL-5R alpha) and a signal-transducing beta-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 alpha mRNA while up-regulating alpha-chain mRNAs for both IL-3R and GM-CSFR as well as the beta-chain mRNA. More 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 stability experiments demonstrate that cytokine-induced inhibition of IL-5R alpha mRNA accumulation occurs at the level of IL-5R alpha gene transcription, whereas enhanced accumulation of mRNAs for IL-3R alpha and the beta-chain results from reduced mRNA degradation. We suggest from these experiments that in human blood eosinophils, IL-5R alpha gene transcription and IL-5R alpha mRNA metabolism can be regulated by mechanisms that are distinct from those used for IL-3R alpha and GM-CSFR alpha.
Wang
P
P
Allergy Department, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. peng.wang@spcorp.com
Wu
P
P
Cheewatrakoolpong
B
B
Myers
J G
JG
Egan
R W
RW
Billah
M M
MM
D002478:Cells, Cultured; D004804:Eosinophils / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics*; D053649:Receptors, Interleukin-5; D014158:Transcription, Genetic / Q000187:drug effects*
D007377:Interleukin-3; D015848:Interleukin-5; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D016178:Granulocyte-Macrophage Colony-Stimulating Factor