Peptides derived from hookworm anti-inflammatory proteins suppress inducible colitis in mice and inflammatory cytokine production by human cells

Cobos, Claudia, Bansal, Paramjit S., Wilson, David T., Jones, Linda, Zhao, Guangzu, Field, Matthew A., Eichenberger, Ramon M., Pickering, Darren A., Ryan, Rachael Y.M., Ratnatunga, Champa N., Miles, John J., Ruscher, Roland, Giacomin, Paul R., Navarro, Severine, Loukas, Alex, and Daly, Norelle L. (2022) Peptides derived from hookworm anti-inflammatory proteins suppress inducible colitis in mice and inflammatory cytokine production by human cells. Frontiers in Medicine, 9. 934852.

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Abstract

A decline in the prevalence of parasites such as hookworms appears to be correlated with the rise in non-communicable inflammatory conditions in people from high- and middle-income countries. This correlation has led to studies that have identified proteins produced by hookworms that can suppress inflammatory bowel disease (IBD) and asthma in animal models. Hookworms secrete a family of abundant netrin-domain containing proteins referred to as AIPs (Anti-Inflammatory Proteins), but there is no information on the structure-function relationships. Here we have applied a downsizing approach to the hookworm AIPs to derive peptides of 20 residues or less, some of which display anti-inflammatory effects when co-cultured with human peripheral blood mononuclear cells and oral therapeutic activity in a chemically induced mouse model of acute colitis. Our results indicate that a conserved helical region is responsible, at least in part, for the anti-inflammatory effects. This helical region has potential in the design of improved leads for treating IBD and possibly other inflammatory conditions.

Item ID: 76415
Item Type: Article (Research - C1)
ISSN: 2296-858X
Keywords: colitis mouse model, inflammation, nuclear magnetic resonance, peptide synthesis, protein structure
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Copyright Information: Copyright © 2022 Cobos, Bansal, Wilson, Jones, Zhao, Field, Eichenberger, Pickering, Ryan, Ratnatunga, Miles, Ruscher, Giacomin, Navarro, Loukas and Daly. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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Funders: Australian Research Council (ARC), National Health and Medical Research Council (NHMRC)
Projects and Grants: Future Fellowship (110100226), Senior Principal Research Fellowship (1117504), Program grant (1037304), Development grant (1178968)
Date Deposited: 14 Nov 2022 02:31
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3205 Medical biochemistry and metabolomics > 320506 Medical biochemistry - proteins and peptides (incl. medical proteomics) @ 50%
34 CHEMICAL SCIENCES > 3404 Medicinal and biomolecular chemistry > 340407 Proteins and peptides @ 50%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 50%
20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 50%
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