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Gene expression analysis in a murine model of allergic asthma reveals overlapping disease and therapy dependent pathways in the lung

The Pharmacogenomics Journal volume 6, pages 141–152 (2006)Cite this article

Abstract

Accumulating evidence in animal models and human asthma support a central role for IL-13 signaling in disease pathogenesis. In order to identify asthma and therapy associated genes, global transcriptional changes were monitored in mouse lung following antigen challenge (ovalbumin (OVA)), either alone or in the presence of a soluble IL-13 antagonist. Changes in whole lung gene expression after instillation of mIL-13 were also measured both in wild type and STAT6 deficient mice. A striking overlap in the gene expression profiles induced by either OVA challenge or mIL-13 was observed, further strengthening the relationship of IL-13 signaling to asthma. Consistent with results from functional studies, a subset of the OVA-induced gene expression was significantly inhibited by a soluble IL-13 antagonist while IL-13-modulated gene expression was completely attenuated in the absence of STAT6-mediated signaling. Results from these experiments greatly expand our understanding of asthma and provide novel molecular targets for therapy and potential biomarkers of IL-13 antagonism.

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Acknowledgements

We thank Sandy Goldman and our colleagues in Molecular Profiling and Biomarker Discovery and Respiratory Disease for support during the course of this work. We are grateful to Maryann Whitley, William Mounts and the Wyeth Bioinformatics Department for continuing support in data analysis and software development. This work was supported by grants to Marsha Wills-Karp including HL58527, Uo1HL66623, HL10342 from the National Institute of Health.

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Author notes

  1. D D Donaldson

    Present address: Millennium Pharmaceuticals Inc., 35 Landsdowne St, Cambridge, MA, 02139, USA

Authors and Affiliations

  1. Department of Molecular Profiling and Biomarker Discovery, Cambridge, MA, USA

    M T Follettie, D K Ellis, V Diesl & A J Dorner

  2. Department of Respiratory Disease, Cambridge, MA, USA

    D D Donaldson, C DeClercq & J P Sypek

  3. Department of BioInformatics, Wyeth Research, Cambridge, MA, USA

    A A Hill

  4. Division of Immunobiology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, OH, USA

    M Wills-Karp

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  1. M T Follettie
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Correspondence to M T Follettie.

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Duality of interest

Wyeth Research has commercial interest in the therapeutic application of Il-13 antagonism.

Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj).

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Follettie, M., Ellis, D., Donaldson, D. et al. Gene expression analysis in a murine model of allergic asthma reveals overlapping disease and therapy dependent pathways in the lung. Pharmacogenomics J 6, 141–152 (2006). https://doi.org/10.1038/sj.tpj.6500357

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