Targeting Inflammation and Oxidative Stress to Improve Outcomes in a TNBS Murine Crohn’s Colitis Model
Anisha Apte,
James R. Bardill,
Jimena Canchis,
Stacy M. Skopp,
Tobias Fauser,
Bailey Lyttle,
Alyssa E. Vaughn,
Sudipta Seal,
David M. Jackson,
Kenneth W. Liechty,
Carlos Zgheib
Affiliations
Anisha Apte
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, Tucson, AZ 85721, USA
James R. Bardill
Department of Surgery, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA
Jimena Canchis
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, Tucson, AZ 85721, USA
Stacy M. Skopp
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, Tucson, AZ 85721, USA
Tobias Fauser
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, Tucson, AZ 85721, USA
Bailey Lyttle
Department of Surgery, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA
Alyssa E. Vaughn
Department of Surgery, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA
Sudipta Seal
Advanced Materials Processing and Analysis Centre, Nanoscience Technology Center, University of Central Florida, Orlando, FL 32827, USA
David M. Jackson
Ceria Therapeutics, Inc., Tucson, AZ 85721, USA
Kenneth W. Liechty
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, Tucson, AZ 85721, USA
Carlos Zgheib
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children’s at Diamond Children’s Medical Center, Tucson, AZ 85721, USA
Inflammation and oxidative stress are implicated in the pathogenesis of Crohn’s disease. Cerium oxide nanoparticle (CNP) conjugated to microRNA 146a (miR146a) (CNP-miR146a) is a novel compound with anti-inflammatory and antioxidative properties. We hypothesized that local administration of CNP-miR146a would improve colitis in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS) mouse model for Crohn’s disease by decreasing colonic inflammation. Balb/c mice were instilled with TNBS enemas to induce colitis. Two days later, the mice received cellulose gel enema, cellulose gel with CNP-miR146a enema, or no treatment. Control mice received initial enemas of 50% ethanol and PBS enemas on day two. The mice were monitored daily for weight loss and clinical disease activity. The mice were euthanized on days two or five to evaluate their miR146a expression, inflammation on histology, and colonic IL-6 and TNF gene expressions and protein concentrations. CNP-miR146a enema successfully increased colonic miR146a expression at 12 h following delivery. At the end of five days from TNBS instillation, the mice treated with CNP-miR146a demonstrated reduced weight loss, improved inflammation scores on histology, and reduced gene expressions and protein concentrations of IL-6 and TNF. The local delivery of CNP-miR146a in a TNBS mouse model of acute Crohn’s colitis dramatically decreased inflammatory signaling, resulting in improved clinical disease.
