RSj16 Protects against DSS-Induced Colitis by Inhibiting the PPAR-? Signaling Pathway.

ABSTRACT: Background: Epidemiologic studies and animal model experiments have shown that parasites have significant modulatory effects on autoimmune disorders, including inflammatory bowel disease (IBD). Recombinant Sj16 (rSj16), a 16-kDa secreted protein of Schistosoma japonicum (S.japonicum) produced by Escherichia coli (E. coli), has been shown to have immunoregulatory effects in vivo and in vitro. In this study, we aimed to determine the effects of rSj16 on dextran sulfate sodium (DSS)-induced colitis. Methods: DSS-induced colitis mice were treated with rSj16. Body weight loss, disease activity index (DAI), myeloperoxidase (MPO) activity levels, colon lengths, macroscopic scores, histopathology findings, inflammatory cytokine levels and regulatory T cell (Treg) subset levels were examined. Moreover, the differential genes expression after treated with rSj16 were sequenced, analyzed and identified. Results: rSj16 attenuated clinical activity of DSS-induced colitis mice, diminished pro-inflammatory cytokine production, up-regulated immunoregulatory cytokine production and increased Treg percentages in DSS-induced colitis mice. Moreover, DSS-induced colitis mice treated with rSj16 displayed changes in the expression levels of specific genes in the colon and show the crucial role of peroxisome proliferator activated receptor ? (PPAR-?) signaling pathway. PPAR-? activation diminished the therapeutic effects of rSj16 in DSS-induced colitis mice, indicating that the PPAR-? signaling pathway plays a crucial role in DSS-induced colitis development. Conclusions: rSj16 has protective effects on DSS-induced colitis, effects mediated mainly by PPAR-? signaling pathway inhibition. The findings of this study suggest that rSj16 may be useful as a therapeutic agent and that PPAR-? may be a new therapeutic target in the treatment of IBD.

SUBMITTER: Wang L 

PROVIDER: S-EPMC5596435 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature