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

Abstract

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.

Inhibitory effects of α-Mangostin on T cell cytokine secretion via ORAI1 calcium channel and K+ channels inhibition

“…Moreover, according to the results of a previous study on the inhibitory effects of α-mangostin on the secretion of cytokines in human peripheral blood mononuclear cells, α-mangostin was reported to inhibit IL-2 secretion by concanavalin A (ConA) stimulation. ConA is known to play a role in producing IL-2 by stimulating TCRs, leading to Ca 2+ signaling and NFAT activation (Fujita et al, 2019;Kasemwattanaroj et al, 2013). This evidence indirectly supports the inhibitory effect on calcium signaling identified in this study.…”