Chemical and cytokine features of innate immunity characterize serum and tissue profiles in inflammatory bowel disease
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Knutson - Chemical and cytokine (2).pdf
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Author(s)
Knutson, Charles G. F.
Mangerich, Aswin
Zeng, Yu
Raczynski, Arkadiusz R.
Liberman, Rosa G.
Kang, Pilsoo
Ye, Wenjie
Prestwich, Erin
Lu, Kun
Wishnok, John S.
Date Issued
June 2013
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Knutson, C. G., A. Mangerich, Y. Zeng, A. R. Raczynski, R. G. Liberman, P. Kang, W. Ye, et al. “Chemical and Cytokine Features of Innate Immunity Characterize Serum and Tissue Profiles in Inflammatory Bowel Disease.” Proceedings of the National Academy of Sciences 110, no. 26 (June 10, 2013): E2332–E2341.
Version
Final published version
Abstract
Inflammatory bowel disease (IBD) arises from inappropriate activation of the mucosal immune system resulting in a state of chronic inflammation with causal links to colon cancer. Helicobacter hepaticus-infected Rag2[superscript −/−] mice emulate many aspects of human IBD, and our recent work using this experimental model highlights the importance of neutrophils in the pathology of colitis. To define molecular mechanisms linking colitis to the identity of disease biomarkers, we performed a translational comparison of protein expression and protein damage products in tissues of mice and human IBD patients. Analysis in inflamed mouse colons identified the neutrophil- and macrophage-derived damage products 3-chlorotyrosine (Cl-Tyr) and 3-nitrotyrosine, both of which increased with disease duration. Analysis also revealed higher Cl-Tyr levels in colon relative to serum in patients with ulcerative colitis and Crohn disease. The DNA chlorination damage product, 5-chloro-2′-deoxycytidine, was quantified in diseased human colon samples and found to be present at levels similar to those in inflamed mouse colons. Multivariate analysis of these markers, together with serum proteins and cytokines, revealed a general signature of activated innate immunity in human IBD. Signatures in ulcerative colitis sera were strongly suggestive of neutrophil activity, and those in Crohn disease and mouse sera were suggestive of both macrophage and neutrophil activity. These data point to innate immunity as a major determinant of serum and tissue profiles and provide insight into IBD disease processes.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Division of Comparative Medicine
Massachusetts Institute of Technology. School of Science
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DOI of Published Version
https://doi.org/10.1073/pnas.1222669110
