Altered beta(2)-adrenergic regulation of T cell activity after allergen challenge in asthma

Irene Heijink, M van den Berge, E Vellenga, JGR de Monchy, DS Postma, HF Kauffman*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

20 Citaten (Scopus)

Samenvatting

Background Airway inflammation in asthma is orchestrated by recruitment of T helper (Th)2 lymphocytes to the lung and subsequent production of Th2-like cytokines upon allergen challenge.

Objective To examine whether allergen-induced dysfunction of the beta(2)-adrenergic receptor (beta(2)-AR) contributes to the enhanced T(h2) cell activity in asthma.

Methods beta(2)-adrenergic regulation of cytokine mRNA expression was studied in alpha-CD3/alpha-CD28-activated peripheral blood lymphocytes from seven asthma patients before and 6 h after allergen challenge, in conjunction with the effects of beta(2)-agonist fenoterol on T cell chemotaxis and signalling pathways.

Results A complete loss of beta(2)-AR control over expression of the Th2 cytokines IL-4, IL-5 and IL-13, but not of the Th1 cytokine IFN-gamma, was observed after allergen challenge. Furthermore, we found impaired beta(2)-AR regulation of T cell migration as well as signal transduction pathways, i.e. the phosphorylation of cyclic adenosine monophosphate-responsive element binding protein and the inhibition of the mitogen-activated protein kinase pathway. The loss of beta(2)-AR control was associated with increased beta-adrenergic receptor kinase expression, which might be involved in beta(2)-AR desensitization. In addition, we demonstrate for the first time that T cells exposed to the chemokine thymus and activation-regulated chemokine show hyporesponsiveness to fenoterol.

Conclusion Our results suggest that allergen-induced loss of beta(2)-AR control, possibly mediated by chemokine release, plays an important role in enhanced Th2-like activity in asthma.

Originele taal-2English
Pagina's (van-tot)1356-1363
Aantal pagina's8
TijdschriftClinical and Experimental Allergy
Volume34
Nummer van het tijdschrift9
DOI's
StatusPublished - sep.-2004

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