Gene expression profile of ovalbumin-induced lung inflammation in a murine model of asthma.
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 oligonucleotide 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 R142571 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.


CONCLUSIONS
The cytokine expression pattern in our data, suggests that the murine model exhibits a predominantlyT 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.
Malik
R
R
Department of Biotechnology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, India.
Priyadarsiny
P
P
Shirumalla
R
R
Soni
R
R
Ray
A
A
Saini
K
K
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000276:immunology; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007109:Immunity / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D010047:Ovalbumin; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D014158:Transcription, Genetic / Q000235:genetics
D018927:Anti-Asthmatic Agents; D010047:Ovalbumin