Involvement of hypoxia-inducible factor-1 HiF(1alpha) in IgE-mediated primary human basophil responses.

Sumbayev, V. and Nicholas, S. and Streatfield, C.L. and Gibbs, B.F. (2009) Involvement of hypoxia-inducible factor-1 HiF(1alpha) in IgE-mediated primary human basophil responses. European Journal of Immunology, 39 (12). pp. 3511-3519. ISSN 0014-2980 . (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1002/eji.200939370

Abstract

Basophils play a pivotal role in regulating chronic allergic inflammation as well as angiogenesis. Here, we show for the first time that IgE-mediated activation of primary human basophils results in protein accumulation of the alpha-subunit of hypoxia-inducible factor 1alpha (HIF-1alpha), which is differentially regulated compared with signals controlling histamine release. HIF-1 facilitates cellular adaptation to hypoxic conditions such as inflammation and tumour growth by controlling glycolysis, angiogenesis and cell adhesion. ERK and p38 MAPK, but not reactive oxygen species (ROS), ASK1 or PI 3-kinase, were critical for IgE-mediated accumulation of HIF-1alpha, although the latter crucially affected degranulation. Abrogating HIF-1alpha expression in basophils using siRNA demonstrated that this protein is essential for vascular endothelial growth factor (VEGF) mRNA expression and, consequently, release of VEGF protein. In addition, HIF-1alpha protein alters IgE-induced ATP depletion in basophils, thus also supporting the production of the pro-allergic cytokine IL-4.

Item Type: Article
Subjects: Q Science
R Medicine
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Bernhard F. Gibbs
Date Deposited: 24 May 2012 08:57
Last Modified: 25 May 2012 11:34
Resource URI: http://kar.kent.ac.uk/id/eprint/29572 (The current URI for this page, for reference purposes)
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