TY - JOUR
T1 - Brugia malayi cystatin therapeutically ameliorates dextran sulfate sodium-induced colitis in mice
AU - Khatri, Vishal
AU - Amdare, Nitin
AU - Tarnekar, Aaditya
AU - Goswami, Kalyan
AU - Reddy, Maryada Venkata Rami
N1 - Publisher Copyright:
© 2015 John Wiley & Sons, Ltd.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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 50μg 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. Conclusion: 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.
AB - 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 50μg 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. Conclusion: 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.
KW - Brugia malayi
KW - DSS colitis
KW - Recombinant cystatin
KW - Therapeutic
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U2 - 10.1111/1751-2980.12290
DO - 10.1111/1751-2980.12290
M3 - Article
C2 - 26358507
AN - SCOPUS:84955315328
SN - 1751-2972
VL - 16
SP - 585
EP - 594
JO - Journal of Digestive Diseases
JF - Journal of Digestive Diseases
IS - 10
ER -