Document Detail

RNA editing of interleukin-12 receptor beta2, 2451 C-to-U (Ala 604 Val) conversion, associated with atopy.
MedLine Citation:
PMID:  15005728     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The production of IgE in B lymphocytes is down-regulated by IFN-gamma. IL-12 induces IFN-gamma production by T lymphocytes and natural killer cells by binding to its specific receptor. RNA editing is a post-transcriptional modification. OBJECTIVE: Here we show that the RNA editing of IL-12 receptor (R) beta2 is associated with atopy. METHODS: Atopic patients and non-atopic healthy controls were studied. Fragments of IL-12R beta2 cDNA and genomic DNA were amplified and sequenced. Furthermore, the function of the IL-12R beta2 chain was investigated. RESULTS: Sequence analysis of the cDNA clones representing IL-12R beta2 mRNA transcripts revealed a C-to-U conversion at nucleotide 2451 (Ala 604 Val) on exon 13 in some atopic patients. Surprisingly, sequence analysis of their genomic DNA showed no 2451 C-to-T (Ala 604 Val) mutation. We concluded that the observed C-to-U mismatch in the cDNA clone is due to a post-transcriptional modification, RNA editing. The C-to-U conversion was observed in 21 (20.6%) of 102 atopic patients, whereas this conversion was observed in only 4 (3.8%) of 104 non-atopic subjects (P<0.001). IFN-gamma production by peripheral blood mononuclear cells (PBMCs) stimulated with IL-12 in the subjects with the C-to-U conversion was significantly lower than that in the subjects without the C-to-U conversion. In atopic patients with the C-to-U conversion, PBMCs faintly showed the tyrosine phosphorylation of Stat4, and the IgE production by PBMCs was not suppressed by IL-12 whereas it was suppressed by IFN-gamma. CONCLUSIONS: The RNA editing of IL-12R beta2, 2451 C-to-U (Ala 604 Val) conversion causes impairment of the IL-12 signal cascade and the subsequent reduction in IFN-gamma production, resulting in the impaired down-regulation of IgE production. This is the first report indicating that atopy is associated with RNA editing.
N Kondo; E Matsui; H Kaneko; M Aoki; Z Kato; T Fukao; K Kasahara; N Morimoto
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology     Volume:  34     ISSN:  0954-7894     ISO Abbreviation:  Clin. Exp. Allergy     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-09     Completed Date:  2004-05-27     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8906443     Medline TA:  Clin Exp Allergy     Country:  England    
Other Details:
Languages:  eng     Pagination:  363-8     Citation Subset:  IM    
Department of Pediatrics, Gifu University School of Medicine, Tsukasa-machi 40, Gifu 500-8705, Japan.
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MeSH Terms
Case-Control Studies
Cells, Cultured
Chi-Square Distribution
Flow Cytometry
Gene Conversion*
Hypersensitivity, Immediate / immunology*
Immunoglobulin E / immunology
Interferon-gamma / immunology
Interleukin-12 / immunology
RNA Editing*
RNA, Messenger / analysis
Receptors, Interleukin / genetics*
Receptors, Interleukin-12
Sequence Analysis, DNA
Signal Transduction
Statistics, Nonparametric
Transfection / methods
Reg. No./Substance:
0/IL12RB2 protein, human; 0/RNA, Messenger; 0/Receptors, Interleukin; 0/Receptors, Interleukin-12; 187348-17-0/Interleukin-12; 37341-29-0/Immunoglobulin E; 82115-62-6/Interferon-gamma

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