Claudio De Simone, Pooja Goswami, Aditya R. Sahu, Govind K. Makharia, Reenu Arora, Dinesh Singal, Vineet Ahuja, Rakesh K. Tandon, Shaman Sood, Vandana Midha, and Ajit Sood
of CRFR2 to inflammation, using a murine model of Crohn's colitis, and to test whether Ucn1 exerts its anti-inflammatory effects via CRFR2. Methods: An intracolonic enema of trinitrobenzene sulfonic acid (TNBS) was used to induce colitis in male C57 mice. An enema of vehicle was given to control group. First, the effect of TNBS was evaluated on the mortality rate and severity of colitis in wild type mice (Wt), CRFR2-/(KO), and CRFR2+/(Ht) mice. Second, Ucn1 was given (ip) when TNBS colitis was induced, to test whether Ucn1 could still exert its anti-inflammatory effects and ameliorate colitis in CRFR2 KO mice. Results: At a 5 mg dose of TNBS, resultant colitis in Wt C57 mice caused a ~20% mortality rate 2 days after injection of TNBS. Surprisingly, 5 mg of TNBS did not cause any mortality in CRFR2-/KO mice. In contrast, TNBS resulted in over 60% mortality rate within 3 days of TNBS injection in CRFR2+/micE. colitis resulted in marked shortening of colon length in from 8.4±0.16 cm (controls) to 6.1±0.27 cm, p