Author(s):
Gressler, Markus ; 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
Date: 2019
Persistent ID: https://hdl.handle.net/1822/67267
Origin: RepositóriUM - Universidade do Minho
Subject(s): 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
Description
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.
