| First Author | Fichtner-Feigl S | Year | 2005 |
| Journal | J Clin Invest | Volume | 115 |
| Issue | 11 | Pages | 3057-71 |
| PubMed ID | 16239967 | Mgi Jnum | J:145688 |
| Mgi Id | MGI:3835759 | Doi | 10.1172/JCI24792 |
| Citation | Fichtner-Feigl S, et al. (2005) Treatment of murine Th1- and Th2-mediated inflammatory bowel disease with NF-kappa B decoy oligonucleotides. J Clin Invest 115(11):3057-71 |
| abstractText | The Th1 and Th2 T cell responses that underlie inflammatory bowel diseases (IBDs) are likely to depend on NF-kappaB transcriptional activity. We explored this possibility in studies in which we determined the capacity of NF-kappaB decoy oligodeoxynucleotides (decoy ODNs) to treat various murine models of IBD. In initial studies, we showed that i.r. (intrarectal) or i.p. administration of decoy ODNs encapsulated in a viral envelope prevented and treated a model of acute trinitrobenzene sulfonic acid-induced (TNBS-induced) colitis, as assessed by clinical course and effect on Th1 cytokine production. In further studies, we showed that NF-kappaB decoy ODNs were also an effective treatment of a model of chronic TNBS-colitis, inhibiting both the production of IL-23/IL-17 and the development of fibrosis that characterizes this model. Treatment of TNBS-induced inflammation by i.r. administration of NF-kappaB decoy ODNs did not inhibit NF-kappaB in extraintestinal organs and resulted in CD4+ T cell apoptosis, suggesting that such treatment is highly focused and durable. Finally, we showed that NF-kappaB decoy ODNs also prevented and treated oxazolone-colitis and thus affect a Th2-mediated inflammatory process. In each case, decoy administration led to inflammation-clearing effects, suggesting a therapeutic potency applicable to human IBD. |
