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Genetic regulation of interleukin-13 production

  • Tineke C. T. M. van der Pouw Kraan
  • John W. Holloway
  • Lucien A. Aarden
  • Jaring S. van der Zee
Chapter
  • 76 Downloads
Part of the Progress in Inflammation Research book series (PIR)

Abstract

The 5q31-33 region contains a number of genes, including IL-13, that could be involved in the aetiology of allergic asthma. Other genes of interest in this region are the Th2 cytokines IL-4 and IL-5; the p40 chain of the Th1 cytokine inducer IL-12; IL-3; IL-9; CD14; the ß2-adrenergic receptor; the corticosteroid receptor and the transcription factors interferon regulatory factor 1 (IRF1) and transcription factor 7 (TCF7). Other diseases such as schistosomiasis may also be (at least partly) controlled by this region. In humans, the severity of infection caused bySchistosomamansoniis linked to a marker on chromosome 5g31 [1]. In mice, resistance to this disease is regulated by Th2 cytokines; in particular, neutralisation of IL-13 leads to reduced pulmonary granuloma formation and total serum IgE levels, while Th2 cytokine production (IL-4, IL-5, and IL-13) remains intact [2]. The important role of Th2 cytokines in human asthma is underscored by the fact that T cells, acquired from bronchial biopsies, display an increased capacity to produce IL-4, IL-5, and IL-13 [3-5]. Interestingly, pulmonary expression of IL-13 is observed in both allergic and non-allergic asthma [6], while IL-4 expression may be more restricted to allergic asthma [7]. Because of their biological effects, IL-4 and IL-13, located at close proximity on 5q31, are very likely candidates to be involved in the inheritance of asthma. Firstly, for an antibody isotype switch to IgE, B cells require stimulation by either IL-4 or IL-13 [8, 9], and secondly these cytokines induce VCAM-1 expression on endothelial cells and pulmonary fibroblasts [10, 11], which may cause the accumulation of eosinophils at the site of the allergic reaction [12]. Recently, other effector functions of IL-4 and IL-13 have been described, independent of IgE and eosinophils.

Keywords

Chronic Obstructive Pulmonary Disease Patient Allergic Asthma Mucus Production Allergic Asthma Patient Transcription Factor Interferon Regulatory Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Basel AG 2002

Authors and Affiliations

  • Tineke C. T. M. van der Pouw Kraan
    • 1
  • John W. Holloway
    • 2
  • Lucien A. Aarden
    • 1
  • Jaring S. van der Zee
    • 3
  1. 1.Department of Molecular Cell Biology VU Medical CenterFree University AmsterdamThe Netherlands
  2. 2.Human Genetics Research Division, University of SouthamptonSouthampton General HospitalSouthamptonUK
  3. 3.Department of PulmonologyAcademic Medical CenterAmsterdamThe Netherlands

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