A Recombinant Cystatin from Ascaris Lumbricoides Has Immunomodulatory Effects

https://doi.org/10.1016/j.jaci.2015.12.878Get rights and content

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Rationale

Helminthiasis may ameliorate inflammatory chronic diseases, such as inflammatory bowel disease (IBD) and asthma. Information about immunomodulators from Ascaris lumbricoides, the most common human helminth worldwide is scarce, but could be important considering the co-evolutionary relationships between helminths and humans. We sought to evaluate the potential immunomodulatory effects of a cystatin from A. lumbricoides on an acute model of IBD.

Methods

From an A. lumbricoides cDNA library we obtained an E. coli produced recombinant cystatin (rAl-CPI). Protease activity inhibition was tested on cathepsin B and papain. Immunomodulatory effects were evaluated at two doses, administered intraperitoneally (0.5 and 0.25 μg/g) on mice with chemically induced (4% Dextran Sodium Sulphate, DSS) - IBD. Body weight, colon length, disease activity index (DAI), histological inflammation score, myeloperoxidase (MPO) activity and gene expression of six

Results

rAl-CPI showed biological activity. The treatment with rAl-CPI significantly reduced DAI, MPO activity and inflammation score, without toxic effects. Also, IL-10 (p<0.0001) and TGFβ (p=0.001) gene overexpression was observed in rAl-CPI treated (both concentrations) compared to DSS-exposed animals and healthy (PBS) group. Furthermore, a significant reduction of IL-6 (p<0.001) and TNFα (p<0.01) expression, key mediators of IBD, was observed. Although lower expression of IL-1β and IL-12 was

Conclusions

rAl-CPI reduces the inflammation in a mouse model of IBD, probably by increasing the expression of anti-inflammatory cytokines and reducing pro-inflammatory ones. The usefulness of this recombinant protein in respiratory inflammation should be further investigated.

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