Gene expression profiling of experimental asthma reveals a possible role of paraoxonase-1 in the disease.
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 T(h)2-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.
Tölgyesi
Gergely
G
Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary.
Molnár
Viktor
V
Semsei
Agnes F
AF
Kiszel
Petra
P
Ungvári
Ildikó
I
Pócza
Péter
P
Wiener
Zoltán
Z
Komlósi
Zsolt I
ZI
Kunos
László
L
Gálffy
Gabriella
G
Losonczy
György
G
Seres
Ildikó
I
Falus
András
A
Szalai
Csaba
C
D000818:Animals; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000502:physiology*; D001249:Asthma / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C
D043303:Aryldialkylphosphatase; C468406:PON1 protein, human