IGF-1 potentiation of IL-4-induced CD23/Fc(epsilon)RII expression in human B cells

Mol Cells. 2003 Jun 30;15(3):307-12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / metabolism*
  • Cell Line
  • Drug Synergism
  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Interleukin-4 / pharmacology*
  • NF-kappa B / metabolism
  • Proline / analogs & derivatives*
  • Proline / pharmacology
  • RNA, Messenger / analysis
  • Receptors, IgE / metabolism*
  • STAT6 Transcription Factor
  • Thiocarbamates / pharmacology
  • Trans-Activators / metabolism
  • Tyrphostins / pharmacology


  • NF-kappa B
  • RNA, Messenger
  • Receptors, IgE
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Thiocarbamates
  • Trans-Activators
  • Tyrphostins
  • prolinedithiocarbamate
  • Interleukin-4
  • Insulin-Like Growth Factor I
  • Proline