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Mediators of Inflammation
Volume 2014, Article ID 917149, 14 pages
Research Article

Antagonizing Arachidonic Acid-Derived Eicosanoids Reduces Inflammatory Th17 and Th1 Cell-Mediated Inflammation and Colitis Severity

1Program in Integrative Nutrition & Complex Diseases, Center for Translational Environmental Health Research, Texas A&M University, College Station, TX, USA
2Department of Nutrition & Food Science, Texas A&M University, College Station, TX, USA
3Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, USA
4University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
5Department of Microbial Pathogenesis and Immunology, Texas A&M University System Health Science Center, College Station, TX, USA

Received 27 March 2014; Accepted 26 June 2014; Published 17 July 2014

Academic Editor: Anshu Agrawal

Copyright © 2014 Jennifer M. Monk 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.


During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA-) derived eicosanoids, such as prostaglandin E2 (PGE2), promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS-) induced colitis. Fat-1 mice contain the 3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, , and IL-23), decreased percentages of Th17 cells and, improved colon injury scores ( ). Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.