Inhibition of IL-4 receptor up-regulation on B cells by antisense oligodeoxynucleotide suppresses IL-4-induced human IgE production.
IL-4 is shown to up-regulate its own receptor (IL-4R) on human lymphocytes, but the functional significance of up-regulated IL-4R is not clear regarding IgE production. This study investigated the possible role of IL-4-induced up-regulation of IL-4R on B cells in the induction of human IgE synthesis by means of antisense strategy. Among three antisense oligodeoxynucleotides designed against the downstream of translation initiation site of IL-4R cDNA, S-oligo 1, complementary to nucleotide 1-24, showed the strongest inhibition of the constitutive expression of IL-4R on Daudi cells. Addition of S-oligo 1 together with IL-4 also decreased the up-regulated but not constitutive levels of IL-4R on peripheral blood B cells without affecting the concomitant enhancement of CD23, CD40, HLA-DR and surface IgM expression, indicating that its effect is specific for IL-4R up-regulation. When S-oligo 1 was added to B cells costimulated with IL-4 and anti-CD40 MoAb, it induced a dose-dependent inhibition of IgE production. This inhibition was accompanied by a decrease in the expression of mature C epsilon transcripts, whereas the accumulation of germ-line C epsilon transcripts was not affected by S-oligo 1. These data suggest that the signal transduction mediated by the up-regulated IL-4R on B cells may be intimately associated with the induction of isotype switching to IgE that leads to mature C epsilon transcription and IgE production.
Ikizawa
K
K
Clinical Research Centre for Allergy, National Sagamihara Hospital, Japan.
Kajiwara
K
K
Koshio
T
T
Matsuura
N
N
Yanagihara
Y
Y
D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001483:Base Sequence; D019013:CD40 Antigens; D017931:DNA Primers / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D005803:Genes, Immunoglobulin; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D007075:Immunoglobulin M / Q000378:metabolism; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D017455:Receptors, IgE / Q000378:metabolism; D018123:Receptors, Interleukin / Q000502:physiology*; D019948:Receptors, Interleukin-4; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D017931:DNA Primers; D006684:HLA-DR Antigens; D007075:Immunoglobulin M; D007139:Immunoglobulin epsilon-Chains; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D017455:Receptors, IgE; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D007073:Immunoglobulin E