Abstract
Arginine deiminase (ADI), an arginine-metabolizing enzyme involved in cell signaling, is dysregulated in multiple inflammatory diseases and cancers. We hypothesized that pegylated ADI (ADI-PEG) provide protection against colitis.
METHODS: Dextran sodium sulfate colitis was induced in IL-10-deficient and BALB/c (WT) mice. ADI-PEG was administered i.p., and inflammatory mediators and pathology were evaluated.
RESULTS: Acute colitis in mice was manifested by increases in inflammatory biomarkers, such as serum amyloid A (SAA, P < 0.001), IL-12 p40, and disease index (3-Fold). In contrast, ADI-PEG significantly decreased clinical disease index, SAA levels, and inflammatory cytokines in blood as well as in colonic explants. Animals developed moderate (2.2 ± 0.3 WT) to severe (3.6 ± 0.5 IL-10 deficient) colonic pathology; and ADI-PEG treatment significantly improved the severity of colitis (P < 0.05). Marked infiltration of CD68+ macrophages and iNOS expression were detected in colonic submucosa in colitic animals but not detected in ADI-PEG-treated animals.
CONCLUSION: ADI-PEG attenuated inflammatory responses by suppression of macrophage infiltration and iNOS expression in colitic animals. ADI-PEG can serve as a potential therapeutic value in IBD.
Document Type
Article
Publication Date
2012
Digital Object Identifier (DOI)
http://dx.doi.org/10.1155/2012/813892
Repository Citation
Oz, Helieh S.; Zhong, Jian; and de Villiers, Willem J. S., "Pegylated Arginine Deiminase Downregulates Colitis in Murine Models" (2012). Physiology Faculty Publications. 54.
https://uknowledge.uky.edu/physiology_facpub/54
Notes/Citation Information
Published in Mediators of Inflammation, v. 2012, article ID 813892, p. 1-7.
Copyright © 2012 Helieh S. Oz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.