UR-1505, a salicylate able to selectively block T-cell activation, shows intestinal anti-inflammatory activity in the chronic phase of the DSS model of rat colitis

Abstract

These results suggest that this compound is a good candidate for inducing remission or maintaining therapies in human inflammatory bowel disease (IBD). Moreover, the different results obtained by UR-1505 in these 2 protocols of colitis induction (acute initial colitis versus established colitis) confirm the importance of selection and optimization of the experimental model to evaluate the drugs to be used in IBD therapy.

The New Salicylate Derivative UR-1505 Modulates the Th2/Humoral Response in a Dextran Sodium Sulphate Model of Colitis That Resembles Ulcerative Colitis

“…The intestinal anti-inflammatory effects of UR-1505 have been supported by our in vitro results demonstrating the specificity of UR-1505 towards T-cell activity, without affecting macrophage activation (2,4,5). However, in those previous studies, we only focused in the Th1- † Both authors contributed equally to the supervision of the study.…”

“…UR-1505 was dissolved in a vehicle consisting of Tween 80 in distilled water (1%) and administered orally by an esophageal catheter. Once rats were killed, different longitudinal colonic segments were used for immunological determinations (4,5). The results reveal that the inflammatory process induced by DSS showed reduced IL-10 and IgA secretions in the colonic specimens, while an increase in IgG levels was observed (Fig.…”

“…UR-1505 has demonstrated the in vivo antiinflammatory effect in both TNBS-and DSS-established colitis, as evidenced histologically by an improvement in the damaged colonic tissue and immunologically by the down-regulation of tumor necrosis factor alpha (TNFα) and interleukin (IL)-1β (4,5). The intestinal anti-inflammatory effects of UR-1505 have been supported by our in vitro results demonstrating the specificity of UR-1505 towards T-cell activity, without affecting macrophage activation (2,4,5).…”

“…In the present study, we further evaluated whether the anti-inflammatory effect of UR-1505 could also be associated with an inhibition of Th2-cytokines, such as IL-5, IL-4, and IL-10, according to the previously described methodology (4,5). Stimulation of splenocytes with concanavalin A (Con A) (5 μg / ml) induced the production of these cytokines (Table 1).…”

A novel tylophorine analog NK-007 ameliorates colitis through inhibition of innate immune response

“…During this period, all mice were examined daily for weight, occult blood and stool consistency. Disease activity index (DAI) was calculated by mean of individual scores of weight loss, stool consistency and occult blood (as shown in Table 1) [23]. Mice with DAI around 2 were randomized into six experimental groups (n = 9 mice) and were treated once a day for 5 days after the last cycle of DSS administration.…”