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Melibiosamine, a novel oligosaccharide, suppresses mitogen-induced IL-2 production via inactivation of NFAT and NFκB in Jurkat cells

d-Glucosamine (GlcNH(2)) and several of its derivatives are known to possess immunosuppressive activities in various immune cell lines. The novel GlcNH(2)-containing oligosaccharide Galα1-6GlcNH(2) (designated melibiosamine; MelNH(2)) is expected to be immunosuppressive also. In Jurkat cells (immort...

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Detalles Bibliográficos
Autores principales: Fujita, Kazuki, Tanaka, Susumu, Iizumi, Kyoichi, Akiyama, Shuri, Uchida, Kaoru, Ogata, Makoto, Aoki, Daichi, Hosomi, Osamu, Kubohara, Yuzuru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580327/
https://www.ncbi.nlm.nih.gov/pubmed/31431927
http://dx.doi.org/10.1016/j.bbrep.2019.100658
Descripción
Sumario:d-Glucosamine (GlcNH(2)) and several of its derivatives are known to possess immunosuppressive activities in various immune cell lines. The novel GlcNH(2)-containing oligosaccharide Galα1-6GlcNH(2) (designated melibiosamine; MelNH(2)) is expected to be immunosuppressive also. In Jurkat cells (immortalized human T lymphocytes), interleukin 2 (IL-2) production (an index of the T-cell immune response) can be induced by stimulation with a mitogen, such as concanavalin A. Here, we compared the effects of GlcNH(2) and MelNH(2) on concanavalin A-induced IL-2 production (CIIP) in Jurkat cells and found that GlcNH(2) and MelNH(2) at millimolar levels both significantly suppressed CIIP without affecting cell viability. When we examined the effects of GlcNH(2) and MelNH(2) on the activation of the three transcription factors required for CIIP—NFAT (nuclear factor of activated T-cells), NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells), and AP-1 (activator protein 1)—we found that GlcNH(2) and MelNH(2) both suppressed CIIP by inhibiting the activation of NFAT and NFκB, but, unlike GlcNH(2), MelNH(2) also promoted the activation of AP-1. These results suggest that MelNH(2) may be a potentially useful lead compound for development as an immunosuppressive or anti-inflammatory drug.