Biomaterial Database

Toll-Like Receptor 7/8 Ligand, S28463, Suppresses Ascaris suum-induced Allergic Asthma in Nonhuman Primates. 2018

Pierre Camateros, and Cynthia Kanagaratham, and Lukáš Najdekr, and Dušan Holub, and Jana Vrbkova, and Lucie Coté, and Jocelyn Fournier, and Jim Gourdon, and David Creery, and Ron Olivenstein, and Frantisek Kopriva, and Tomáš Adam, and David Friedecký, and Petr Džubák, and Marian Hajdúch, and Danuta Radzioch

1 Faculty of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.

S28463 (S28), a ligand for Toll-like receptor 7/8, has been shown to have antiinflammatory properties in rodent models of allergic asthma. The principle goal of this study was to assess whether these antiinflammatory effects can also be observed in a nonhuman primate (NHP) model of allergic asthma. NHPs were sensitized then challenged with natural allergen, Ascaris suum extract. The animals were treated with S28 orally before each allergen challenge. The protective effect of S28 in NHPs was assessed by measuring various asthma-related phenotypes. We also characterized the metabolomic and proteomic signatures of the lung environment and plasma to identify markers associated with the disease and treatment. Our data demonstrate that clinically relevant parameters, such as wheal and flare response, blood IgE levels, recruitment of white blood cells to the bronchoalveolar space, and lung responsiveness, are decreased in the S28-treated allergic NHPs compared with nontreated allergic NHPs. Furthermore, we also identified markers that can distinguish allergic from nonallergic or allergic and drug-treated NHPs, such as metabolites, phosphocreatine and glutathione, in the plasma and BAL fluid, respectively; and inflammatory cytokines, IL-5 and IL-13, in the bronchoalveolar lavage fluid. Our preclinical study demonstrates that S28 has potential as a treatment for allergic asthma in primate species closely related to humans. Combined with our previous findings, we demonstrate that S28 is effective in different models of asthma and in different species, and has the antiinflammatory properties clinically relevant for the treatment of allergic asthma.

UI	MeSH Term	Description	Entries
D008252	Macaca fascicularis	A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula.	Burmese Long-Tailed Macaque,Crab-Eating Monkey,Cynomolgus Monkey,M. f. aurea,M. fascicularis,Macaca fascicularis aurea,Monkey, Crab-Eating,Monkey, Cynomolgus,Crab-Eating Macaque,Burmese Long Tailed Macaque,Crab Eating Macaque,Crab Eating Monkey,Crab-Eating Macaques,Crab-Eating Monkeys,Cynomolgus Monkeys,Long-Tailed Macaque, Burmese,Macaque, Burmese Long-Tailed,Macaque, Crab-Eating,Monkey, Crab Eating
D000485	Allergens	Antigen-type substances that produce immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).	Allergen
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001249	Asthma	A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).	Asthma, Bronchial,Bronchial Asthma,Asthmas
D015801	Helminth Proteins	Proteins found in any species of helminth.	Helminth Protein,Protein, Helminth,Proteins, Helminth
D015848	Interleukin-5	A cytokine that promotes differentiation and activation of EOSINOPHILS. It also triggers activated B-LYMPHOCYTES to differentiate into IMMUNOGLOBULIN-secreting cells.	B-Cell Growth Factor-II,Eosinophil Differentiation Factor,IL-5,T-Cell Replacing Factor,BCGF-II,Differentiation Factor, Eosinophil,IL5,T-Cell-Replacing Factor,B Cell Growth Factor II,Interleukin 5,Replacing Factor, T-Cell,T Cell Replacing Factor
D017165	Ascaris suum	A species of parasitic nematode usually found in domestic pigs and a few other animals. Human infection can also occur, presumably as result of handling pig manure, and can lead to intestinal obstruction.	Ascaris suums,suum, Ascaris
D051199	Toll-Like Receptor 7	A pattern recognition receptor that binds several forms of imidazo-quinoline including the antiviral compound Imiquimod.	TLR7 Receptor,Receptor, TLR7,Toll Like Receptor 7
D051200	Toll-Like Receptor 8	A pattern recognition receptor that recognizes GUANOSINE and URIDINE-rich single-stranded RNA.	TLR8 Receptor,Receptor, TLR8,Toll Like Receptor 8
D018793	Interleukin-13	A cytokine synthesized by T-LYMPHOCYTES that produces proliferation, immunoglobulin isotype switching, and immunoglobulin production by immature B-LYMPHOCYTES. It appears to play a role in regulating inflammatory and immune responses.	IL-13,IL 13,IL13,Interleukin 13