Substance-P Ameliorates Dextran Sodium Sulfate-Induced Intestinal Damage by Preserving Tissue Barrier Function

ABSTRACT

Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease. Thus, the modulation of intestinal integrity and immune responses in IBD can be the critical factor to be considered to reduce the severity of damages. Substance-P (SP), endogenous peptide to be involved in cell proliferation, migration and immune modulation, can exert the therapeutic effect on diverse diseases including cornea damage, rheumatoid arthritis and diabetic complications. SP was found to elevate expression of junctional molecule. Considering the function of SP reported previously, it was inferred that SP is capable of exert the beneficial effect of SP on intestinal diseases by controlling intestinal structure as well as immune responses. In this study, we explored the therapeutic effect of SP on dextran sodium sulfate-induced intestine damage by injecting SP. The effects of SP were evaluated by analyzing crypt structures, proliferating cell pool and infiltration of immune cells. DSS treatment provoked abnormal immune response and disruption of intestine epithelial barrier. However, co-treatment of SP obviously blocked the development of intestinal damages by declining inflammatory responses and sustaining intestinal structure more intact. The treatment of SP to chronic damages also promoted intestinal regeneration by preserving the integrity of colon tissue. Moreover, DSS-induced reduction of epithelial junctional molecule was obviously inhibited by SP treatment in vitro. Taken together, our data indicate that SP can reduce intestinal damages, possibly by modulating barrier structure and immune response. Our results propose SP as candidate therapeutics in intestinal damages.