Crude extract of hydatid laminated layer from Echinococcus granulosus cyst attenuates mucosal intestinal damage and inflammatory responses in Dextran Sulfate Sodium induced colitis in mice

Abstract

BackgroundInflammatory bowel disease is an immunologically mediated disease. Notably, it is less common in countries where there is a greater risk of exposure to helminths. In our study, we examined the modulatory effect of the laminated layer extracted from the cyst wall of a helminth parasite, Echinococcus granulosus, on dextran sulfate sodium (DSS)-induced colitis in mice.MethodsAn acute colitis was induced in BALB/c mice using 2.5% w/v DSS in drinking water. The crude extract of E. granulosus laminated layer was injected intraperitoneally daily, starting 3 days before colitis induction. The Disease Activity Index was monitored daily, colon length and weight were measured and histological scores were evaluated. Nitric oxide (NO) and cytokine levels (interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10)) were assessed by enzyme-linked immunosorbent assay. In addition, the colonic expression of inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) was examined. Statistical analyses were performed by one-way analysis of variance and the survival rate was analyzed by the long rank test.ResultsHydatid laminated layer pretreatment significantly improved the clinical symptoms and histological scores (*** p < 0.01) observed during DSS-induced colitis and maintained mucus production by goblet cells. Furthermore, treatment with hydatid laminated layer caused a significant decrease in NO, IFN-γ (** p < 0.01) and TNF-α production (* p < 0.05) and an increase in IL-10 production. These results were associated with localized downregulation of iNOS and NF-κB expression.ConclusionsOur results demonstrate the potent anti-inflammatory effects of hydatid laminated layer. Furthermore, preventive treatment with the laminated layer played a beneficial role in maintaining the integrity of the intestinal mucosal barrier against DSS-induced injury.

Larval Echinococcus multilocularis infection reduces dextran sulphate sodium‐induced colitis in mice by attenuating T helper type 1/type 17‐mediated immune reactions

“…Previous experiments using a mouse model of cystic echinococcosis ( E. granulosus infection) have suggested that concomitant infection with E. granulosus improved the clinical score, ameliorated the DAI, and prevented the shortening of the colon in experimental DSS‐induced colitis; such improvement was associated with a reduced nitric oxide and TNF‐ α production in the plasma of experimental E. granulosus ‐infected mice with DSS‐induced colitis and decreased inducible nitric oxide synthase and nuclear factor‐ κ B expression in colonic tissue. It is interesting to note that a crude extract of the laminated layer from an E. granulosus cyst was as able as active E. granulosus infection to attenuate mucosal intestinal damage and inflammatory responses in DSS‐induced colitis in mice; in these experiments using the laminated layer, the authors also focused on macrophage‐dependent mechanisms, and confirmed the reduced nitric oxide production and inducible nitric oxide synthase expression in the colon as well as reduced TNF‐ α production. However, no complementary studies of the T‐cell‐related immunoregulatory mechanisms were performed.…”

“…The results of our first experiments fully confirm our hypothesis; taken together, our observations suggest that a pre–established E. multilocularis infection protects mice from DSS‐induced colitis. DSS‐exposed E. multilocularis ‐infected mice exhibited significantly less severe colitis than those animals without E. multilocularis infection: colonic improvement included maintained colorectal lengths, and microscopically normal mucosal structures with a nearly normal number and size of goblet cells secreting mucus, in marked contrast to non‐infected animals with DSS‐induced colitis, suggesting that E. multilocularis , like other helminths, can help in preserving/restoring these cells . Goblet cells are involved in regulating both the mucosal barrier and the relative composition of the luminal microbiota by mucin production .…”

“…DSS‐exposed E. multilocularis ‐infected mice exhibited significantly less severe colitis than those animals without E. multilocularis infection: colonic improvement included maintained colorectal lengths, and microscopically normal mucosal structures with a nearly normal number and size of goblet cells secreting mucus, in marked contrast to non‐infected animals with DSS‐induced colitis, suggesting that E. multilocularis , like other helminths, can help in preserving/restoring these cells . Goblet cells are involved in regulating both the mucosal barrier and the relative composition of the luminal microbiota by mucin production . The production of mucus by these cells could limit bacterial access to epithelial cells and prevent chronic inflammation …”

Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases

“…In both patients and animal models of IBD, a positive correlation between the overproduction of pro-inflammatory cytokines (e.g., IL-1b, TNF-α, IFN-γ) and an overexpression of iNOS was found. This expression was primarily detected in the lamina propria mononuclear cells and the colon epithelial cells of the inflamed mucosa [6,16,17,27,30,71,72] . Several studies conducted on a dextran sulfate sodium (DSS)-induced experimental model of colitis in BALB/c mice indicated that the neutralization of endogenous TNF-α and/or IFN-γ ameliorated the chronic colitis and concomitantly decreased the generation of NO.…”

Cytokines and Nitric Oxide in Immunopathogenesis of IBD and Potential Therapeutic Approaches

“…Indeed, immunity to helminth is TH2-type response dependent on the secretion of antiinflammatory cytokines (IL-4, IL-5, IL-13, and IL-9) and the induction of Tregs. Experimental studies demonstrated that helminthes infection attenuate damaging TH1-/TH17-driven inflammatory responses through the induction of regulatory responses [99][100][101] …”