Gene expression analysis in a murine model of allergic asthma reveals overlapping disease and therapy dependent pathways in the lung

Follettie, Maximillian T.; Ellis, Debra; Donaldson, Deb; Hill, Andrew; Diesl, Veronica; DeClercq, Charlene; Sypek, Joseph P.; Dorner, Andrew J.; Wills‐Karp, Marsha

doi:10.1038/sj.tpj.6500357

Cited by 24 publications

(26 citation statements)

References 37 publications

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“…However, there are contradictory opinions on the exact role of AMCase in asthma. AMCase gene expression is increased during allergen challenge in ova-sensitized mice (Zhu et al, 2004;Follettie et al, 2006). These observations led to the hypothesis that AMCase contributes to the pathogenesis of Th2 immune responses (Zhu et al, 2004).…”

Section: Discussionmentioning

confidence: 95%

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Evolutionary and biochemical differences between human and monkey acidic mammalian chitinases

Krykbaev

Fitz

Reddy

et al. 2010

Gene

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Section: Discussionmentioning

confidence: 95%

“…In humans and mice it is expressed at high levels in the stomach, and is also expressed in the lung, where it is further induced upon antigen stimulation (Boot et al, 2001;Zhu et al, 2004;Follettie et al, 2006). In a mouse model of asthma, blockade of AMCase prevents lung inflammation and airway hyperreactivity (AHR) (Zhu et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Evolutionary and biochemical differences between human and monkey acidic mammalian chitinases

Krykbaev

Fitz

Reddy

et al. 2010

Gene

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“…Shibamori and colleagues (37) used Der f extract in repeated intranasal sensitizations, and observed increased AHR after a single challenge with 100 mg of Der f. Tournoy and Schou (26) achieved increased AHR in this strain by sensitizing mice with Der p 1 plus alum with a chronic challenge protocol (Days [14][15][16][17][18][19][20]. Importantly, others showed that the addition of adjuvant, namely alum, initiates a distinct inflammatory response involving the inflammosome (38).…”

Section: Discussionmentioning

confidence: 99%

“…Hence 34% (54/161) of the genes were shared by both strains. The list of shared genes includes Arg1, Agr2, Clca3, Muc5ac, Ccl8, Ccl11, Chi3L3, Chi3L4, Chia, Scin, Retnla, Retnlb, Timp, Ear11, Mgl1, Saa3, Serpina3n, and Slc6a24, which were previously described in murine studies (15)(16)(17)(18)(19)(20)(21)(22), adding further support to a role for these genes in allergic airway disease. A subset of these genes was evaluated and confirmed by quantitative RT-PCR (Table E4).…”

Section: Gene Expression Analysis Reveals Shared and Distinct Patternmentioning

confidence: 99%

Strain-Dependent Genomic Factors Affect Allergen-Induced Airway Hyperresponsiveness in Mice

Kelada

Wilson

Tavarez

et al. 2011

Am J Respir Cell Mol Biol

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Asthma is etiologically and clinically heterogeneous, making the genomic basis of asthma difficult to identify. We exploited the straindependence of a murine model of allergic airway disease to identify different genomic responses in the lung. BALB/cJ and C57BL/6J mice were sensitized with the immunodominant allergen from the Dermatophagoides pteronyssinus species of house dust mite (Der p 1), without exogenous adjuvant, and the mice then underwent a single challenge with Der p 1. Allergic inflammation, serum antibody titers, mucous metaplasia, and airway hyperresponsiveness were evaluated 72 hours after airway challenge. Whole-lung gene expression analyses were conducted to identify genomic responses to allergen challenge. Der p 1-challenged BALB/cJ mice produced all the key features of allergic airway disease. In comparison, C57BL/6J mice produced exaggerated Th2-biased responses and inflammation, but exhibited an unexpected decrease in airway hyperresponsiveness compared with control mice. Lung gene expression analysis revealed genes that were shared by both strains and a set of down-regulated genes unique to C57BL/6J mice, including several G-protein-coupled receptors involved in airway smooth muscle contraction, most notably the M2 muscarinic receptor, which we show is expressed in airway smooth muscle and was decreased at the protein level after challenge with Der p 1. Murine strain-dependent genomic responses in the lung offer insights into the different biological pathways that develop after allergen challenge. This study of two different murine strains demonstrates that inflammation and airway hyperresponsiveness can be decoupled, and suggests that the downmodulation of expression of G-protein-coupled receptors involved in regulating airway smooth muscle contraction may contribute to this dissociation.

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“…Using animal models of allergic airway disease, investigators applied DNA microarrays to identify potential regulators of asthmatic airway inflammation such as C5 (3), ARG1 (4), ADAM8 (5), SPRR2 (6) as well as to explore the pathways activated by IL13 and STAT6 during the development of allergen-induced lung inflammation (7)(8)(9). Transcriptional analysis of the response to IL-13, allergen challenge, syncytial virus infection, and corticosteroids in epithelial cells identified multiple and rarely overlapping genes (10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

A Functional and Regulatory Map of Asthma

Novershtern

Barnett-Itzhaki²,

Manor³

et al. 2008

Am J Respir Cell Mol Biol

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The prevalence and morbidity of asthma, a chronic inflammatory airway disease, is increasing. Animal models provide a meaningful but limited view of the mechanisms of asthma in humans. A systemslevel view of asthma that integrates multiple levels of molecular and functional information is needed. For this, we compiled a gene expression compendium from five publicly available mouse microarray datasets and a gene knowledge base of 4,305 gene annotation sets. Using this collection we generated a high-level map of the functional themes that characterize animal models of asthma, dominated by innate and adaptive immune response. We used Module Networks analysis to identify co-regulated gene modules. The resulting modules reflect four distinct responses to treatment, including early response, general induction, repression, and IL-13-dependent response. One module with a persistent induction in response to treatment is mainly composed of genes with suggested roles in asthma, suggesting a similar role for other module members. Analysis of IL-13-dependent response using protein interaction networks highlights a role for TGF-b1 as a key regulator of asthma. Our analysis demonstrates the discovery potential of systems-level approaches and provides a framework for applying such approaches to asthma.Keywords: house dust mite; IL-13; ovalbumin; systems biology; TGF-b Asthma is a chronic lung disease characterized by airway inflammation, hyperresponsiveness, remodeling, and obstruction (1). The lung phenotype in asthma is believed to be determined by the interaction of the environment with the patient's genetic background (2). This interaction leads to a dramatic change in the airway microenvironment that includes activation of inflammatory pathways, recruitment of immune cells that are not usually present in the airway, and a dramatic change in the phenotype of airway resident cells. While individual changes in many of these factors may generate components of the asthmatic phenotype, it is the converging effects of these pathways on recruited and altered cells that determine the patient's disease.The advent of high-throughput technologies for gene and protein profiling has greatly improved our ability to characterize the behavior of genes and proteins in health and disease. Using animal models of allergic airway disease, investigators applied DNA microarrays to identify potential regulators of asthmatic airway inflammation such as C5 (3), ARG1 (4), ADAM8 (5), SPRR2 (6) as well as to explore the pathways activated by IL13 and STAT6 during the development of allergen-induced lung inflammation (7-9). Transcriptional analysis of the response to IL-13, allergen challenge, syncytial virus infection, and corticosteroids in epithelial cells identified multiple and rarely overlapping genes (10-14). While many of these studies used elegant experimental approaches to dissect pathways and to identify and validate potential novel key regulatory molecules, the majority of their insights were obtained using statistical methods that select...

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Gene expression analysis in a murine model of allergic asthma reveals overlapping disease and therapy dependent pathways in the lung

Cited by 24 publications

References 37 publications

Evolutionary and biochemical differences between human and monkey acidic mammalian chitinases

Evolutionary and biochemical differences between human and monkey acidic mammalian chitinases

Strain-Dependent Genomic Factors Affect Allergen-Induced Airway Hyperresponsiveness in Mice

A Functional and Regulatory Map of Asthma

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