Cysteine protease of Clonorchis sinensis alleviates DSS-induced colitis in mice

Abstract

Background Currently, inflammatory bowel disease (IBD) has become a global chronic idiopathic disease with ever-rising morbidity and prevalence. Accumulating evidence supports the IBD-hygiene hypothesis that helminths and their derivatives have potential therapeutic value for IBD. Clonorchis sinensis (C. sinensis) mainly elicit Th2/Treg-dominated immune responses to maintain long-term parasitism in the host. This study aimed to evaluate the therapeutic effects of cysteine protease (CsCP) and adult crude antigen (CsCA) of C. sinensis, and C. sinensis (Cs) infection on DSS-induced colitis mice. Methods BALB/c mice were given 5% DSS daily for 7 days to induce colitis. During this period, mice were treated with rCsCP, CsCA or dexamethasone (DXM) every day, or Cs infection which was established in advance. Changes in body weight, disease activity index (DAI), colon lengths, macroscopic scores, histopathological findings, myeloperoxidase (MPO) activity levels, regulatory T cell (Treg) subset levels, colon gene expression levels, serum cytokine levels, and biochemical indexes were measured. Results Compared with Cs infection, rCsCP and CsCA alleviated the disease activity of acute colitis more significant without causing abnormal blood biochemical indexes. In comparison, rCsCP was superior to CsCA in attenuating colonic pathological symptoms, enhancing the proportion of Treg cells in spleens and mesenteric lymph nodes, and improving the secretion of inflammatory-related cytokines (e.g., IL-2, IL-4, IL-10 and IL-13) in serum. Combined with RNA-seq data, it was revealed that CsCA might up-regulate the genes related to C-type lectin receptor and intestinal mucosal repair related signal pathways (e.g., Cd209d, F13a1 and Cckbr) to reduce colon inflammation and benefit intestinal mucosal repair. Dissimilarly, rCsCP ameliorated colitis mainly through stimulating innate immunity, such as Toll like receptor (TLR) signaling pathway, down-regulating the expression of inflammatory cytokines (e.g., IL-12b, IL-23r and IL-7), thereby restraining the differentiation of Th1/Th17 cells. Conclusions Both rCsCP and CsCA showed good therapeutic effects on the treatment of acute colitis, but rCsCP is a better choice. rCsCP is a safe, effective, readily available and promising therapeutic agent against IBD mainly by activating innate immunity and regulating the IL-12/IL-23r axis.

Antagomir of miR-31-5p modulates macrophage polarization via the AMPK/SIRT1/NLRP3 signaling pathway to protect against DSS-induced colitis in mice

“…Dexamethasone is commonly used for the treatment of colitis in mice and humans. In this study, it was employed as a positive control reagent for mice and administered via intraperitoneal injection [ 19 ]. We found that compared with the DSS group, the administration of miR-31-5p antagomir significantly reduced the DAI score [ 20 ] ( P < 0.05) ( Figure 3C ).…”

The prophylactic and therapeutic impact of Trichinella spiralis larvae excretory secretory antigens- loaded Ca-BTC metal organic frameworks on induced murine colitis

“…This can be explained by the reduction in inflammation of AA-induced colitis offered by intraperitoneal delivery of T. spiralis -produced antigens. In mice treated with Clonorchis sinensis cysteine protease, Xie et al (2022) also observed a significantly higher survival rate for dextran sulfate sodium-induced colitis.…”

Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis

“…Mounting evidence indicates that C . sinensis infection drives Th2 immune responses and facilitates the production of the cytokines IL-13, TGF-β, IL-10 and IL-4 [ 53 , 54 ], which have been implicated in promoting cancer stemness [ 55 , 56 ]. Carlo De Salvo et al uncovered the importance of eosinophils in the early cascade leading to intestinalized metaplasia in gastritis-prone mice, suggesting a potential mechanism that contributes to the inflammation-metaplasia-dysplasia-carcinoma sequence [ 57 ].…”