Recombinant cystatin from Schistosoma japonicum therapeutically ameliorates CLP-induced Sepsis in mice
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摘要
Objectives: Helminth or it's derived protein are potent inducers of T helper type 2(Th2) response and have a regulatory role, notably on allergic or autoimmune diseases. Now it's immunomodulation in host has also been shown to have therapeutic implications in sepsis which is characterised by the aberrant production of pro-inflammatory. Herein we have evaluated the therapeutic effect of recombinant cystatin from Schistosoma japonicum(r Sjcystatin) in a mice model of polymicrobial sepsis. Methods: The mice model with sepsis was established with cecal ligation and puncture(CLP). BALB/c mice were treated intraperitoneally(i.p.) with rB mC ys(10, 25 or 50 μg/dose) 0.5 h after the CLP operation, and persistent observation was performed for 72 h. Blood samples and tissues were collected at 12 h after CLP. Cytokines in serum were measured by ELISA. The pathological damage of liver and kidney tissue were stained with hematoxylin-eosin(HE), and the function of liver and kidney was examined 12 h after the CLP operation by fully automatic chemistry analyzer. Results: Treatment with r Sjcystatin in mice ameliorated the pathological damage degree and the increased serum levels of ALT, AST, BUN, and Cr caused by CLP-induced sepsis in liver and kidney of mice. While the level of TNF-α, IL-1β and IL-6 was down-regulated, the IL-10 and TGF-β expression were up-regulated in the serum of CLP-induced sepsis mice treated with r Sjcystatin. The amelioration effect in CLP-induced sepsis mice was in a dose-dependent manner.Conclusions: The results of this study indicate rS jcystatin can counterbalance exacerbated pro-inflammatory immune responses that occur during sepsis, improving survival. The anti-inflammatory effect of r Sjcystatin provides evidential support for this protein to be used as a promising therapeutic agent in sepsis.
Objectives: Helminth or it's derived protein are potent inducers of T helper type 2(Th2) response and have a regulatory role, notably on allergic or autoimmune diseases. Now it's immunomodulation in host has also been shown to have therapeutic implications in sepsis which is characterised by the aberrant production of pro-inflammatory. Herein we have evaluated the therapeutic effect of recombinant cystatin from Schistosoma japonicum(r Sjcystatin) in a mice model of polymicrobial sepsis. Methods: The mice model with sepsis was established with cecal ligation and puncture(CLP). BALB/c mice were treated intraperitoneally(i.p.) with rB mC ys(10, 25 or 50 μg/dose) 0.5 h after the CLP operation, and persistent observation was performed for 72 h. Blood samples and tissues were collected at 12 h after CLP. Cytokines in serum were measured by ELISA. The pathological damage of liver and kidney tissue were stained with hematoxylin-eosin(HE), and the function of liver and kidney was examined 12 h after the CLP operation by fully automatic chemistry analyzer. Results: Treatment with r Sjcystatin in mice ameliorated the pathological damage degree and the increased serum levels of ALT, AST, BUN, and Cr caused by CLP-induced sepsis in liver and kidney of mice. While the level of TNF-α, IL-1β and IL-6 was down-regulated, the IL-10 and TGF-β expression were up-regulated in the serum of CLP-induced sepsis mice treated with r Sjcystatin. The amelioration effect in CLP-induced sepsis mice was in a dose-dependent manner.Conclusions: The results of this study indicate rS jcystatin can counterbalance exacerbated pro-inflammatory immune responses that occur during sepsis, improving survival. The anti-inflammatory effect of r Sjcystatin provides evidential support for this protein to be used as a promising therapeutic agent in sepsis.
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