A network-based analysis of the late-phase reaction of the skin - 17/08/11
, Michael A. Langston, PhD b, Mikael Adner, PhD c, Bengt Andersson, MD, PhD d, Åsa Torinssson-Naluai, PhD e, Lars Olaf Cardell, MD, PhD c
Reprint requests: Mikael Benson, MD, PhD, Queen Silvia Children’s Hospital, SE-41685 Gothenburg, Sweden.Gothenburg and Malmö, Sweden, and Knoxville, Tenn
Abstract |
Background |
The late-phase reaction (LPR) of the skin is an in vivo model of allergic inflammation.
Objective |
We sought to identify disease-associated pathways in the LPR using a network-based analysis.
Methods |
The LPR was examined by means of DNA microarray analysis of skin biopsy specimens from 10 patients with allergic rhinitis and 10 healthy control subjects. The results were further analyzed in 2 different materials consisting of nasal fluids and allergen-challenged CD4+ T cells from patients with allergic rhinitis.
Results |
The DNA microarray analysis revealed several genes of known relevance to allergy. The eosinophil marker Charcot-Leyden crystal protein (CLC) that encodes Charcot-Leyden crystal protein differed most in expression. A network-based analysis showed upregulation of IL-4– and CCL4-dependent pathways and downregulation of a TGF-β–induced pathway. CCL4 is expressed by CD4+ T cells and chemotactic for eosinophils. We hypothesized that allergen induces release of CCL4 from TH2 cells and that this contributes to influx of eosinophils. Further analysis showed increase of CCL4 protein in nasal fluids from allergic patients during the season. Allergen challenge of PBMCs resulted in proliferation of TH2 cells and increased production of CCL4 in CD4+ T cells from allergic patients. An analysis of the DNA microarray data revealed a significant correlation between CCL4 and the eosinophil marker CLC.
Conclusion |
A network-based analysis of the LPR showed increased activity of IL-4– and CCL4- dependent pathways and downregulation of the TGF-β–induced pathway. Allergen-induced release of CCL4 from TH2 cells might contribute to influx of eosinophils during the LPR.
Clinical implications |
Involvement of multiple interacting pathways indicates that it might be difficult to identify one single mediator as a biomarker or drug target in allergic inflammation.
Le texte complet de cet article est disponible en PDF.Key words : DNA microarrays, gene expression, late-phase reaction
Abbreviations used : CLC, CT, IPA, LPR
Plan
| Supported by grants from the Swedish Medical Research Council and the Swedish Asthma and Allergy Foundation. Disclosure of potential conflict of interest: All authors have received grants from the Swedish Research Council, Asthma and Allergy Foundation. |
Vol 118 - N° 1
P. 220-225 - juillet 2006 Retour au numéro
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