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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.
J Immunol. 1998 May 01; 160(9):4427-32.JI

Abstract

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.

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Authors+Show Affiliations

Wang P
Allergy Department, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. peng.wang@spcorp.com
Wu P
No affiliation info available
Cheewatrakoolpong B
No affiliation info available
Myers JG
No affiliation info available
Egan RW
No affiliation info available
Billah MM
No affiliation info available

MeSH

Cells, CulturedEosinophilsGene Expression RegulationGranulocyte-Macrophage Colony-Stimulating FactorHumansInterleukin-3Interleukin-5Receptors, InterleukinReceptors, Interleukin-5Transcription, Genetic

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9574547

Citation

Wang, P, et al. "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." Journal of Immunology (Baltimore, Md. : 1950), vol. 160, no. 9, 1998, pp. 4427-32.
Wang P, Wu P, Cheewatrakoolpong B, et al. 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. J Immunol. 1998;160(9):4427-32.
Wang, P., Wu, P., Cheewatrakoolpong, B., Myers, J. G., Egan, R. W., & Billah, M. M. (1998). 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. Journal of Immunology (Baltimore, Md. : 1950), 160(9), 4427-32.
Wang P, et al. 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. J Immunol. 1998 May 1;160(9):4427-32. PubMed PMID: 9574547.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Wang,P, AU - Wu,P, AU - Cheewatrakoolpong,B, AU - Myers,J G, AU - Egan,R W, AU - Billah,M M, PY - 1998/5/9/pubmed PY - 1998/5/9/medline PY - 1998/5/9/entrez SP - 4427 EP - 32 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 160 IS - 9 N2 - 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. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9574547/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_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9574547 DB - PRIME DP - Unbound Medicine ER -
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