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    Biomarkers of Disease and Treatment in Murine and Cynomolgus Models of Chronic Asthma

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    Author
    Louten, Jennifer; Mattson, Jeanine D.; Malinao, Maria-Christina; Li, Ying; Emson, Claire; Vega, Felix; Wardle, Robert L.; Van Scott, Michael R.; Fick, Robert B.; McClanahan, Terrill K.; de Waal Malefyt, Rene; Beaumont, Maribel
    Abstract
    Background Biomarkers facilitate early detection of disease and measurement of therapeutic efficacy, both at clinical and experimental levels. Recent advances in analytics and disease models allow comprehensive screening for biomarkers in complex diseases, such as asthma, that was previously not feasible. Objective Using murine and nonhuman primate (NHP) models of asthma, identify biomarkers associated with early and chronic stages of asthma and responses to steroid treatment. Methods The total protein content from thymic stromal lymphopoietin transgenic (TSLP Tg) mouse BAL fluid was ascertained by shotgun proteomics analysis. A subset of these potential markers was further analyzed in BAL fluid, BAL cell mRNA, and lung tissue mRNA during the stages of asthma and following corticosteroid treatment. Validation was conducted in murine and NHP models of allergic asthma. Results Over 40 proteins were increased in the BAL fluid of TSLP Tg mice that were also detected by qRT-PCR in lung tissue and BAL cells, as well as in OVA-sensitive mice and house dust mite-sensitive NHP. Previously undescribed as asthma biomarkers, KLK1, Reg3γ, ITLN2, and LTF were modulated in asthmatic mice, and Clca3, Chi3l4 (YM2), and Ear11 were the first lung biomarkers to increase during disease and the last biomarkers to decline in response to therapy. In contrast, GP-39, LCN2, sICAM-1, YM1, Epx, Mmp12, and Klk1 were good indicators of early therapeutic intervention. In NHP, AMCase, sICAM-1, CLCA1, and GP-39 were reduced upon treatment with corticosteroids. Conclusions and clinical relevance These results significantly advance our understanding of the biomarkers present in various tissue compartments in animal models of asthma, including those induced early during asthma and modulated with therapeutic intervention, and show that BAL cells (or their surrogate, induced sputum cells) are a viable choice for biomarker examination.
    URI
    http://hdl.handle.net/10342/5783
    Subject
     biomarkers; asthma; proximal fluid/tissue; corticosteroids; asthma treatment; nonhuman primate; murine 
    Date
    2012
    Citation:
    APA:
    Louten, Jennifer, & Mattson, Jeanine D., & Malinao, Maria-Christina, & Li, Ying, & Emson, Claire, & Vega, Felix, & Wardle, Robert L., & Van Scott, Michael R., & Fick, Robert B., & McClanahan, Terrill K., & de Waal Malefyt, Rene, & Beaumont, Maribel. (January 2012). Biomarkers of Disease and Treatment in Murine and Cynomolgus Models of Chronic Asthma. Biomarker Insights, (87-104. Retrieved from http://hdl.handle.net/10342/5783

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    MLA:
    Louten, Jennifer, and Mattson, Jeanine D., and Malinao, Maria-Christina, and Li, Ying, and Emson, Claire, and Vega, Felix, and Wardle, Robert L., and Van Scott, Michael R., and Fick, Robert B., and McClanahan, Terrill K., and de Waal Malefyt, Rene, and Beaumont, Maribel. "Biomarkers of Disease and Treatment in Murine and Cynomolgus Models of Chronic Asthma". Biomarker Insights. . (87-104.), January 2012. March 03, 2021. http://hdl.handle.net/10342/5783.
    Chicago:
    Louten, Jennifer and Mattson, Jeanine D. and Malinao, Maria-Christina and Li, Ying and Emson, Claire and Vega, Felix and Wardle, Robert L. and Van Scott, Michael R. and Fick, Robert B. and McClanahan, Terrill K. and de Waal Malefyt, Rene and Beaumont, Maribel, "Biomarkers of Disease and Treatment in Murine and Cynomolgus Models of Chronic Asthma," Biomarker Insights 7, no. (January 2012), http://hdl.handle.net/10342/5783 (accessed March 03, 2021).
    AMA:
    Louten, Jennifer, Mattson, Jeanine D., Malinao, Maria-Christina, Li, Ying, Emson, Claire, Vega, Felix, Wardle, Robert L., Van Scott, Michael R., Fick, Robert B., McClanahan, Terrill K., de Waal Malefyt, Rene, Beaumont, Maribel. Biomarkers of Disease and Treatment in Murine and Cynomolgus Models of Chronic Asthma. Biomarker Insights. January 2012; 7() 87-104. http://hdl.handle.net/10342/5783. Accessed March 03, 2021.
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