Brady, Karen and Fitzgerald, Stephen and Ingvarsson, Sigurdur and Borrebaeck, Carl A.K. and Moynagh, Paul N. (2001) CD40 Employs p38 MAP Kinase in IgE Isotype Switching. Biochemical and Biophysical Research Communications, 289 (1). pp. 276-281. ISSN 0006-291X

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Abstract

IgE switching requires the prior induction of Ce germline transcripts which is mediated by the concerted binding of STAT-6 and NFkB to the Ce promoter. These transcription factors are regulated by IL-4 and CD40, respectively. However the latter can effect other signaling pathways and the present study explores the role of p38 MAPK in induction of Ce germline transcripts. CD40 and IL-4, both alone and in synergy, were initially shown to activate the Ce promoter in a B cell lymphoma cell line. Under the same conditions CD40 caused activation of p38 MAPK, whereas IL-4 was ineffective. The p38 MAPK inhibitor, SB203580, and a dominant negative form of p38 MAPK decreased the CD40 activation of the Ce promoter by reducing the ability of CD40 to increase the transactivation potential of NFkB. This study suggests that p38 MAPK is crucially important in mediating CD40 activation of NFkB which acts to induce Ce germline transcripts, ultimately facilitating IgE switching.

Item Type:	Article
Additional Information:	The work was supported by the European Commission 4th Framework Biotechnology Programme (BIO4 CT96 0246), 5th Framework Biotechnology Programme (QLK3-CT-2000-00270), and Enterprise Ireland.
Keywords:	CD40; IgE; isotype switching; allergy; p38 MAP kinase; NFkB;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	7187
Identification Number:	https://doi.org/10.1006/bbrc.2001.5968
Depositing User:	Professor Paul Moynagh
Date Deposited:	15 Jul 2016 11:06
Journal or Publication Title:	Biochemical and Biophysical Research Communications
Publisher:	Academic Press
Refereed:	Yes
Funders:	European Commission 4th Framework Biotechnology Programme, European Commission 5th Framework Biotechnology Programme, Enterprise Ireland (EI)
URI:	http://www.sciencedirect.com/
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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