Therapeutic effect of Schistosoma japonicum cystatin on bacterial sepsis in mice
| العنوان: | Therapeutic effect of Schistosoma japonicum cystatin on bacterial sepsis in mice |
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| المؤلفون: | Dapeng Qiu, Qiang Fang, Hui Zhang, Nan Li, Xing-Zhi Chen, Liang Chu, Xiaodi Yang, Shushu Wang, Bin Zhan, Jilong Shen, Yong-Kun Wan, Huihui Li, Wen-Xin He |
| المصدر: | Parasites & Vectors, Vol 10, Iss 1, Pp 1-13 (2017) Parasites & Vectors |
| بيانات النشر: | BMC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Lipopolysaccharides, Lipopolysaccharide, Aspartate transaminase, Inflammation, Cysteine Proteinase Inhibitors, Nitric Oxide, T-Lymphocytes, Regulatory, Schistosoma japonicum, lcsh:Infectious and parasitic diseases, Sepsis, Transforming Growth Factor beta1, Immunomodulation, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Immune system, medicine, Animals, lcsh:RC109-216, Cecum, Kidney, Mice, Inbred BALB C, biology, Interleukin-6, Tumor Necrosis Factor-alpha, Research, Macrophages, Cystatin, Cecal ligation and puncture, medicine.disease, Cystatins, Recombinant Proteins, Interleukin-10, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, chemistry, Alanine transaminase, Bacteremia, Immunology, biology.protein, Cytokines, Parasitology, medicine.symptom, 030215 immunology |
| الوصف: | Background Sepsis is a life-threatening complication of an infection and remains one of the leading causes of mortality in surgical patients. Bacteremia induces excessive inflammatory responses that result in multiple organ damage. Chronic helminth infection and helminth-derived materials have been found to immunomodulate host immune system to reduce inflammation against some allergic or inflammatory diseases. Schistosoma japonicum cystatin (Sj-Cys) is a cysteine protease inhibitor that induces regulatory T-cells and a potential immunomodulatory. The effect of Sj-Cys on reducing sepsis inflammation and mortality was investigated. Methods Sepsis was induced in BALB/c mice using cecal ligation and puncture (CLP), followed by intraperitoneal injection of different doses (10, 25 or 50 μg) of recombinant Sj-Cys (rSj-Cys). The therapeutic effect of rSj-Cys on sepsis was evaluated by observing the survival rates of mice for 96 h after CLP and the pathological injury of liver, kidney and lung by measuring the levels of alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN) and creatinine (Cr) in sera and the tissue sections pathology, and the expression of MyD88 in liver, kidney and lung tissues. The immunological mechanism was investigated by examining pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and IL-10 and TGF-β1 in mice sera and in culture of macrophages stimulated by lipopolysaccharides (LPS). Results rSj-Cys treatment provided significant therapeutic effects on CLP-induced sepsis in mice demonstrated with increased survival rates, alleviated overall disease severity and tissue injury of liver, kidney and lung. The rSj-Cys conferred therapeutic efficacy was associated with upregualted IL-10 and TGF-β1 cytokines and reduced pro-inflammatory cytokines TNF-α, IL-6, IL-1β. MyD88 expression in liver, kidney and lung tissues of rSj-Cys-treated mice was reduced. In vitro assay with macrophages also showed that rSj-Cys inhibited the release of pro-inflammatory cytokines and mediator nitric oxide (NO) after being stimulated by lipopolysaccharide (LPS). Conclusions The results suggest the anti-inflammatory potential of rSj-Cys as a promising therapeutic agent on sepsis. The immunological mechanism underlying its therapeutic effect may involve the downregulation of pro-inflammatory cytokines and upregulation of IL-10 and TGF-β1 cytokines possibly via downregulation of the TLR adaptor-transducer MyD88 pathway. The findings suggest rSj-Cys is a potential therapeutic agent for sepsis and other inflammatory diseases. |
| اللغة: | English |
| تدمد: | 1756-3305 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fb84092db0344a80062b9a5852b2e851 http://link.springer.com/article/10.1186/s13071-017-2162-0 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fb84092db0344a80062b9a5852b2e851 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 17563305 |
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