title: Therapeutic potential of recombinant cystatin from Schistosoma japonicum in TNBS-induced experimental colitis of mice.
abstract: BACKGROUND
  Helminth infections and their components have been shown to have a protective effect on autoimmune diseases. The isolated purified protein from Schisotosoma japonicum and its potential therapeutic effect on trinitrobenzene sulfonic acid (TNBS)-induced colitis could provide an alternative way to treat inflammatory bowel disease (IBDs).
  
  
  METHODS
  Colitis was induced in Balb/c mice by rectal administration of 2.5% TNBS, followed by intraperitoneal injection of rSjcystatin 50 μg at 6 h and 24 h afterwards. The inflammation was monitored by recording weight change, stool character and bleeding, colon length, macroscopic score (MAO), microscopic score (MIO), myeloperoxidase activity (MPO) and disease activity index (DAI). The potential underlying mechanism was investigated by examining cytokine profiles including Th1 (IFNγ), Th2 (IL-4), Th17 (IL-17A) and Treg subsets from lymphocytes of spleen, mesenteric lymph nodes (MLN) and intestinal lamina propria mononuclear cells (LPMCs) by flow cytometry. The mRNA relative expressions of the cytokines in splenocytes and MLN were analysed by quantitative real time reverse-transcriptase polymerase chain reaction (qRT-PCR). Simultaneously, the concentrations of the cytokines in the colon homogenate supernatants were tested by enzyme-linked immunosorbent assay (ELISA) and key transcription factors were detected by Western blotting.
  
  
  RESULTS
  Administration of rSjcystatin significantly reduced inflammatory parameters and ameliorated the severity of the TNBS-induced colitis through decreasing IFNγ in three organs and lifting the level of IL-4, IL-13, IL-10, and TGF-β in the colon tissues, with uptrending Tregs in the MLN and LPMC.
  
  
  CONCLUSIONS
  The findings provide evidence that rSjcystatin has a therapeutic potential for diminishing colitis inflammation in Balb/c mice. The immunological mechanism may involve the down-regulation of Th1 response and up-regulation of Th2 and Tregs in the MLN and colon.
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei, 230022, China. 9799175@qq.com.|Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, Hefei, 230022, China. 9799175@qq.com.|Pediatrics Department of Affiliated Provincial Hospital, Anhui Medical University, Hefei, 230001, China. 9799175@qq.com.
authors.forename: Shushu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei, 230022, China. 979129104@qq.com.|Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, Hefei, 230022, China. 979129104@qq.com.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Microbiology and Parasitology, Bengbu Medical College; Anhui Key Laboratory of Infection and Immunity, Bengbu, 233000, Anhui, China. yxd_qf@163.com.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Pediatrics Department of Affiliated Provincial Hospital, Anhui Medical University, Hefei, 230001, China. wxswsswbq@163.com.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Laboratory Diagnosis, the Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China. 2745yanke@sina.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Yan
authors.affiliation: Department of Laboratory Diagnosis, the Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China. zrzhong@126.com.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Laboratory Diagnosis, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. ww1991@126.com.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Laboratory Diagnosis, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. XYHong1964@163.com.
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei, 230022, China. 445993975@qq.com.|Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, Hefei, 230022, China. 445993975@qq.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei, 230022, China. lf0825@live.com.|Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, Hefei, 230022, China. lf0825@live.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Immunology, Anhui Medical University, Hefei, 230022, China. shenjilong53@126.com.|Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, Hefei, 230022, China. shenjilong53@126.com.
authors.forename: Jilong
authors.initials: J
authors.lastname: Shen
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D003106:Colon / Q000276:immunology; D015891:Cystatins / Q000627:therapeutic use*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy; D007413:Intestinal Mucosa / Q000276:immunology; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D012549:Schistosoma japonicum / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects
chemical_list: D015891:Cystatins; D016207:Cytokines; D011994:Recombinant Proteins; D014302:Trinitrobenzenesulfonic Acid