Abstract
Background: Asthma is a chronic inflammatory disease that is associated with airway hyperresponsiveness, tissue remodeling, and airway obstruction, and that involves coordinate expression of multiple inflammatory genes in the lungs.
Objective: To evaluate the gene expression pattern in a mouse model of asthma and assess the effect of a new drug, R142571, on the gene expression profile.
Methods: Lung tissue from ovalbumin-sensitized mice was used to examine gene expression on the CodeLink oligonucleoticle mouse 20 K bioarray platform. Data were validated for some genes by semiquantitative reverse-transcriptase polymerase chain reaction.
Results: Of the 19 736 genes represented on the microarray, expression of 378 genes was differentially regulated (215 upregulated and 163 downregulated), with at least a 2-fold change in expression (P<.05). The differentially regulated transcripts included genes known to be involved in several different biological processes, including signaling, DNA-dependent transcriptional regulation, immune response, proteolysis, and peptidolysis. Cluster analysis of the differentially regulated genes showed that at least 16 were downregulated by RI 42571 treatment at both of the doses used (1 and 10 mg/kg). In addition, 46 and 29 genes were downregulated at doses of 10 mg/kg and 1 mg/kg, respectively, as compared to the animals treated with vehicle.
Conclusion: The cytokine expression pattern in our data, suggests that the murine model exhibits a predominantly T helper 2-type response, as observed in asthmatic human subjects. Based on this study, we suggest that this mouse model would be an appropriate system for screening new drug molecules for treatment of atopic asthma.