Up-regulation of interleukin-4 receptor expression by interleukin-4 and CD40 ligation via tyrosine kinase-dependent pathway

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Title
Up-regulation of interleukin-4 receptor expression by interleukin-4 and CD40 ligation via tyrosine kinase-dependent pathway
Author(s)
Hyun Il Kim; Eui Young So; Suk Ran Yoon; Mi Young Han; Choong Eun Lee
Bibliographic Citation
BMB Reports, vol. 31, no. 1, pp. 83-88
Publication Year
1998
Abstract
Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4 (IL-4) and CD40 ligation in B cell activation, we have examined the effect of CD40 cross-linking on the IL-4 receptor expression in human B cells using anti-CD40 antibody. We observed that IL-4 and anti-CD40 both induce IL-4 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in a significant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4 action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.
Keyword
Anti-CD40 AntibodyCD40 LigationInterleukin-4Interleukin-4 ReceptorTyrosine Kinase
ISSN
1225-8687
Publisher
Korea Soc-Assoc-Inst
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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