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International Immunology Advance Access originally published online on June 25, 2009
International Immunology 2009 21(8):967-975; doi:10.1093/intimm/dxp063
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Gene expression profiling of experimental asthma reveals a possible role of paraoxonase-1 in the disease

Gergely Tölgyesi1, Viktor Molnár1, Ágnes F. Semsei1, Petra Kiszel1, Ildikó Ungvári1, Péter Pócza1, Zoltán Wiener1, Zsolt I. Komlósi2, László Kunos2, Gabriella Gálffy2, György Losonczy2, Ildikó Seres3, András Falus1,4 and Csaba Szalai4,5,6

1 Department of Genetics, Cell and Immunobiology
2 Department of Pulmonology, Semmelweis University, Budapest, Hungary
3 First Department of Medicine, University of Debrecen, Medical and Health Science Centre, Debrecen Hungary
4 Section of Inflammation Biology and Immunogenomics, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
5 Central Laboratory, Heim Pál Pediatric Hospital, Budapest H-1958, Hungary
6 Csertex Research Laboratory, Budapest, Hungary

Correspondence to: C. Szalai; E-mail: szalaics{at}gmail.com

In this study, we aimed to identify novel genes involved in experimental and human asthma, importance of which has not yet been recognized. In an ovalbumin-induced murine model of asthma, we applied microarray gene expression analysis at different time points after allergen challenges. Advanced statistical methods were used to relate gene expression changes to cellular processes and to integrate our results into multiple levels of information available in public databases. At 4 h after the first allergen challenge, gene expression pattern reflected mainly an acute, but non-atopic, inflammatory response and strong chemotactic activity. At 24 h after the third allergen challenge, gene set enrichment analysis revealed significant over-representation of gene sets corresponding to Th2-type inflammation models. Among the top down-regulated transcripts, an anti-oxidant enzyme, paraoxonase-1 (PON1), was identified. In human asthmatic patients, we found that serum PON1 activity was reduced at exacerbation, but increased parallel with improving asthma symptoms. PON1 gene polymorphisms did not influence the susceptibility to the disease. Our observations suggest that an altered PON1 activity might be involved in the pathogenesis of asthma, and serum PON1 level might be used for following up the effect of therapy.

Keywords: airway inflammation, gene set enrichment analysis, microarray, oxidative stress, paraoxonase-1

Transmitting editor: C. Terhorst

Received 9 March 2009, accepted 29 May 2009.


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