Peptide fragments of cystatin protein from filarial parasite has potent anti-inflammatory effect on DSS-induced colitis in mouse

Le résumé fourni par la source

Abstract The therapeutic potential of filarial parasite derived recombinant cystatin was reported previously by our group in the mouse model of colitis. We showed that cystatin-treatment elevated IL-10+FoxP3+Tregs, IgM+B1a cells and AAMs in the colon and peritoneal cavity. In this study, we attempted to identify the therapeutically active peptide(s) of cystatin. Total length of cystatin is 157 aa. We first synthesized three 40-mer peptides of cystatin. 25μg of peptide 1, 2 or 3 was injected i.p. into groups of 10 mice each on days 3–6 following DSS-administration. Control mice received DMSO only. Mice that received whole cystatin protein remained as positive control. Following treatment, clinical and pathological disease parameters were determined. Our results show that treatment with peptide 1 and 2 significantly ameliorated the inflammatory responses in the colitis mice and significantly reversed the gross and histopathological changes in the colon. However, peptide 3 had no effect in alleviating the colitis symptoms. Analysis of the colon tissue showed that the myeloperoxidase activity was significantly (p<0.005) decreased following peptide 1 and 2 treatment. The frequencies of F4/80+TLR-4+CD11c+ peritoneal macrophages were significantly decreased in colitis mice. There was also reduced infiltration of LY6G+ cells and MPO+ cells and increased FoxP3+Tregs counts in the colon tissue of these animals compared to the controls. These attenuative effects of both peptide 1 and 2 in colitis was comparable to the whole cystatin protein treatment. These studies thus demonstrate that peptide 1 and peptide 2 of the parasite cystatin can be potentially developed as a peptide therapy for colitis. Study supported by Blazer Foundation of Rockford.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.