title: Brugia malayi cystatin therapeutically ameliorates dextran sulfate sodium-induced colitis in mice.
abstract: OBJECTIVE
  Helminth immunomodulation in the host has been shown to have therapeutic implications in inflammatory bowel diseases. In this study we aimed to evaluate the therapeutic effect of Brugia malayi recombinant cystatin (rBmCys) in a dose-dependent manner on dextran sulfate sodium (DSS)-induced colitis in mice.
  
  
  METHODS
  The anti-inflammatory activity of rBmCys on mice peritoneal exudate cells was initially analyzed in vitro. BALB/c mice were fed with 5% DSS for 7 days to induce colitis. The colitis mice were treated intraperitoneally with rBmCys (10, 25 or 50 µg for the three different groups of mice) on days 1, 3 and 5 of the DSS administration. Disease severity was assessed by the disease activity index (DAI) and macroscopic and histopathological scores of colon and myeloperoxidase activity in colonic mucosa. Cytokine profiles were measured in sera and cultured splenocytes of treated mice followed by stimulation with rBmCys.
  
  
  RESULTS
  rBmCys showed anti-inflammatory activity in vitro. Treatment of DSS-induced colitis with rBmCys in mice ameliorated the overall disease severity as reflected by a significant reduction in weight loss, the DAI, mucosal edema, colon damage and myeloperoxidase activity of the colonic mucosa. While the mRNA expressions of IFN-γ, TNF-α, interleukin (IL)-5, IL-6 and IL-17 were downregulated, IL-10 expression was upregulated in the splenocytes of colitis mice treated with rBmCys. The amelioration of DSS-induced colitis occurred in a dose-dependent manner.
  
  
  CONCLUSIONS
  The results of this study indicate an anti-inflammatory potential of rBmCys and provide evidence for using this protein as a promising therapeutic agent in ulcerative colitis.
authors.affiliation: Department of Biochemistry & JB Tropical Disease Research Center, Mahatma Gandhi Institute of Medical Sciences, Maharashtra, India.
authors.forename: Vishal
authors.initials: V
authors.lastname: Khatri
authors.affiliation: Department of Biochemistry & JB Tropical Disease Research Center, Mahatma Gandhi Institute of Medical Sciences, Maharashtra, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Amdare
authors.affiliation: Department of Anatomy, Mahatma Gandhi Institute of Medical Sciences, Maharashtra, India.
authors.forename: Aaditya
authors.initials: A
authors.lastname: Tarnekar
authors.affiliation: Department of Biochemistry & JB Tropical Disease Research Center, Mahatma Gandhi Institute of Medical Sciences, Maharashtra, India.
authors.forename: Kalyan
authors.initials: K
authors.lastname: Goswami
authors.affiliation: Department of Biochemistry & JB Tropical Disease Research Center, Mahatma Gandhi Institute of Medical Sciences, Maharashtra, India.
authors.forename: Maryada Venkata Rami
authors.initials: MV
authors.lastname: Reddy
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017178:Brugia malayi / Q000737:chemistry*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects; D015891:Cystatins / Q000627:therapeutic use*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D015801:Helminth Proteins / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D015891:Cystatins; D015801:Helminth Proteins; C556062:IL10 protein, mouse; D020381:Interleukin-17; D015848:Interleukin-5; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D016753:Interleukin-10; D007371:Interferon-gamma; D016264:Dextran Sulfate; D009195:Peroxidase
keywords: Brugia malayi; DSS colitis; recombinant cystatin; therapeutic