IGF-1 potentiation of IL-4-induced CD23/Fc(epsilon)RII expression in human B cells.
Interleukin-4 (IL-4) is a major cytokine regulating IgE production and IgE response. Neuroendocrine growth factors, such as growth hormone and insulin-like growth factor (IGF-1), also modulate IgE production by human B cells. We report that in both human primary immune cells and established B cell lines, IGF-1 increased expression of the IL-4-induced type II IgE receptor (Fc(epsilon)RII/CD23). This effect was also seen at the mRNA level. IGF-1 increased the activity of signal transducer and activator of transcription 6 (STAT6) in response to IL-4, and activated NF-(kappa)B. STAT6 and NF-(kappa)B are major transcription factors controlling CD23 expression. The tyrosine kinase inhibitor, tyrphostin, abolished both IL-4- and IL-4 plus IGF-1-mediated induction of STAT6 and the subsequent CD23 expression. In contrast, pyrrolidine dithiocarbamate (PDTC), an NF-(kappa)B inhibitor, only suppressed the enhancing effect of IGF-1 on IL-4-induced CD23 expression. Our data suggest that IGF-1 modulates CD23 gene expression by affecting the STAT6 and NF-(kappa)B pathways. Regulation of CD23 by IGF-1 may have an important implication for the immunomodulatory potential of IGF-1, and may provide a new therapeutic target for allergy and other hypersensitivity reactions involving an excessive IgE response.
Kim
Jeong-Ho
JH
Laboratory of Immunology, Department of Biological Science and Institute for Basic Science, SungKyunKwan University, Suwon 440-746, Korea.
Park
Hyun-Hee
HH
Lee
Choong-Eun
CE
D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D004357:Drug Synergism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D017455:Receptors, IgE / Q000378:metabolism*; D050800:STAT6 Transcription Factor; D013859:Thiocarbamates / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
D016328:NF-kappa B; D012333:RNA, Messenger; D017455:Receptors, IgE; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D013859:Thiocarbamates; D015534:Trans-Activators; D020032:Tyrphostins; C066229:prolinedithiocarbamate; D015847:Interleukin-4; D007334:Insulin-Like Growth Factor I; D011392:Proline