PT  - JOURNAL ARTICLE
AU  - Zsolt István Komlosi
AU  - Ildikό Ungvári
AU  - Έva Hadadi
AU  - Viktor Virág
AU  - Katalin Έder
AU  - Gergely Tölgyesi
AU  - András Falus
AU  - György Losonczy
TI  - Investigation for candidate genes of glucocorticoid resistance by genome-wide gene expression profiling in animal model of asthma
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p711
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p711.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p711.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - The prevalence of impaired glucocorticoid (GC) responsiveness or GC resistance (GR) is 5-10% among asthma patients, even so 50% of asthma-related health care costs are spent on these cases. We have developed a murine model of asthma with GR (Clin.Exp.Allergy 2006;36:951). Ovalbumin (Ova) challenge, preceded by intranasal lipopolysaccharide priming, resulted in more severe eosinophil inflammation in Ova sensitized BALB/c mice (LPS/OVA) than Ova provocation alone (OVA). Moreover, the airway inflammation was resistant to dexamethasone (Dex) treatment in LPS/OVA mice. To further investigate the mechanisms of GR in this model, we have performed 20 whole mouse gene expression microarrays (44K; Agilent, St.Clara, USA). Total lung tissue mRNA expression of GC sensitive (OVA) and resistant (LPS/OVA) mice, as well as their Dex-treated counterparts (OVA+Dex and LPS/OVA+Dex) were compared with the gene expression profile of control (C) animals using two sample t test (n=4/group). The obtained gene lists were further dissected by GeneSpring GX (Agilent), considering only the significantly altered genes (p<0.01 vs. C) that show at least 2-fold up or down regulation. From these genes 23 were identified to be GR-related, i.e. were found in the common cluster of uniquely changed genes of LPS/OVA (but not OVA) and LPS/OVA+Dex (but not OVA+Dex) mice. Members of known asthma-related (eg. Serpine1) and GR pathways (eg. transforming growth factor β-2) were found to be involved in our model supporting relevance of this model to human disease. We have also nominated new candidate genes as potential therapeutic targets for GR in asthma. Funded by Hungarian Respiratory Society.