Gene expression analysis in a murine model of allergic asthma reveals overlapping disease and therapy dependent pathways in the lung.
Accumulating evidence in animal models and human asthma support a central role for IL-13 signaling in disease pathogenesis. In order to identify asthma and therapy associated genes, global transcriptional changes were monitored in mouse lung following antigen challenge (ovalbumin (OVA)), either alone or in the presence of a soluble IL-13 antagonist. Changes in whole lung gene expression after instillation of mIL-13 were also measured both in wild type and STAT6 deficient mice. A striking overlap in the gene expression profiles induced by either OVA challenge or mIL-13 was observed, further strengthening the relationship of IL-13 signaling to asthma. Consistent with results from functional studies, a subset of the OVA-induced gene expression was significantly inhibited by a soluble IL-13 antagonist while IL-13-modulated gene expression was completely attenuated in the absence of STAT6-mediated signaling. Results from these experiments greatly expand our understanding of asthma and provide novel molecular targets for therapy and potential biomarkers of IL-13 antagonism.
Follettie
M T
MT
Department of Molecular Profiling and Biomarker Discovery, Cambridge, MA 02140, USA. MFollettie@Wyeth.com
Ellis
D K
DK
Donaldson
D D
DD
Hill
A A
AA
Diesl
V
V
DeClercq
C
C
Sypek
J P
JP
Dorner
A J
AJ
Wills-Karp
M
M
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D020869:Gene Expression Profiling; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D050800:STAT6 Transcription Factor / Q000235:genetics
D000941:Antigens; D018793:Interleukin-13; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D010047:Ovalbumin