AUTHOR=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. TITLE=Peptides derived from hookworm anti-inflammatory proteins suppress inducible colitis in mice and inflammatory cytokine production by human cells JOURNAL=Frontiers in Medicine VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.934852 DOI=10.3389/fmed.2022.934852 ISSN=2296-858X 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.