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;Daly, Norelle L.

Guangzu Zhao Matt Field Darren Pickering Rachael Ryan Roland Ruscher Paul Giacomin Alex Loukas Norelle Daly

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.

Journal

Frontiers in Medicine

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2296-858X

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Frontiers Research Foundation

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DOI

10.3389/fmed.2022.934852