Definition of the anti-inflammatory oligosaccharides derived from the galactosaminogalactan (GAG) from Aspergillus fumigatus

• Autor(a) principal: Gressler, Markus
• Data de Publicação: 2019
• Outros Autores: Heddergott, Christoph, N'Go, Inés C., Renga, Giorgia, Oikonomou, Vasilis, Moretti, Silvia, Coddeville, Bernadette, Gaifem, Joana, Silvestre, Ricardo Jorge Leal, Romani, Luigina, Latgé, Jean-Paul, Fontaine, Thierry
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/67267
• topic: Animals; Anti-Inflammatory Agents; Aspergillus fumigatus; Colitis; Dextran Sulfate; Humans; Interleukin 1 Receptor Antagonist Protein; Leukocytes, Mononuclear; Mice; Oligosaccharides; Polysaccharides; Polysaccharides, Bacterial; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Galactosaminogalactan; IL-Ra; Anti-inflammatory response; Glycodrug; Ciências Médicas::Medicina Básica; Science & Technology

Galactosaminogalactan (GAG) is an insoluble aminosugar polymer produced by Aspergillus fumigatus and has anti-inflammatory properties. Here, the minimum glycosidic sequences required for the induction of IL-1Ra by peripheral blood mononuclear cells (PBMCs) was investigated. Using chemical degradation of native GAG to isolate soluble oligomers, we have found that the de-N-acetylation of galactosamine residues and the size of oligomer are critical for the in vitro immune response. A minimal oligomer size of 20 galactosamine residues is required for the anti-inflammatory response but the presence of galactose residues is not necessary. In a Dextran sulfate induced colitis mouse model, a fraction of de-N-acetylated oligomers of 13 < dp < 20 rescue inflammatory damage like the native GAG polymer in an IL-1Ra dependent pathway. Our results demonstrate the therapeutic suitability of water-soluble GAG oligosaccharides in IL-1 mediated hyper-inflammatory diseases and suggest that α-1,4-galactosamine oligomers chemically synthesized could represent new anti-inflammatory glycodrugs.