Search

D-Allose is classified as a 'rare sugar,' i.e., part of the group of monosaccharides that are present in low quantities in the natural world. D-Allose has been demonstrated to exert many physiological functions. The effects of the rare sugars on immune responses are largely unexplored. Here, we investigated the physiological effects of D-allose on murine dendritic cells' cytokine production. When plasmacytoid dendritic cells (pDCs) were stimulated with a Toll-like receptor 7 (TLR7) ligand, a single-stranded RNA (ssRNA), or a TLR9 ligand, CpG DNA, in the medium containing D-allose, the productions of both interferon-alpha (IFN-α) and interleukin (IL)-12p40 were severely decreased. In contrast, a normal production of these cytokines was observed when pDCs were stimulated with other TLR7 ligands, an imidazoquinoline, or a guanosine analog. In contrast to the pDCs, conventional dendritic cells (cDCs) produced IL-12p40 and tumor necrosis factor-alpha (TNF-α) in response to an imidazoquinoline or CpG DNA even though D-allose was present in the medium. D-Allose did not induce pDC death, and not inhibit the endocytic uptake of fluorophore-labeled CpG DNA into pDCs. These results suggested that D-allose exerts its inhibitory effects after CpG DNA is internalized. We analyzed the TLR7/9 signal-induced activation of downstream signaling molecules in pDCs and observed that when pDCs were stimulated with a ssRNA or CpG DNA, the phosphorylation status of the MAPK family, which includes Erk1/2, JNK/SAPK, and p38 MAPK, was attenuated in the presence of D-allose compared to D-glucose controls. The stimulation of pDCs with an imidazoquinoline induced a strong phosphorylation of these MAPK family members even in the presence of D-allose. These findings reveal that D-allose can inhibit the cytokine production by pDCs stimulated with ssRNA or CpG DNA via an attenuation of the phosphorylation of MAPK family members. • D-allose has a selective inhibitory effect on cytokine production by pDCs. • Endocytosis of TLR ligand into pDCs was not inhibited in the presence of D-allose. • TLR signal-induced activation of MAPKs was attenuated in the presence of D-allose. [ABSTRACT FROM AUTHOR]

Abstract: Nuclear magnetic resonance and relaxation measurements of the 59Co nuclei for the well-defined field-aligned powder of the triangular lattice superconductor Na x CoO2 · yH2O with a nearly optimal composition for the transition temperature T c have been performed. Detailed analyses indicate that the Knight shifts for the directions parallel and perpendicular to the CoO2 plane and the spin-lattice relaxation rates, taken by making an inevitable deterioration of specimen minimal, are significantly smaller than most of the data reported to date, and that this compound is classified into one of the unconventional spin-singlet superconductors as suggested by recent works for single crystals with a lower T c. A small enhancement of two-dimensional antiferromagnetic spin correlations at some nonzero wave vector may emerge near T c. [Copyright &y& Elsevier]

Plasmacytoid dendritic cells (pDCs) are characterized by an exclusive expression of nucleic acid sensing Toll-like receptor 7 (TLR7) and TLR9, and production of high amounts of type I interferon (IFN) in response to TLR7/9 signaling. This function is crucial for both antiviral immunity and the pathogenesis of autoimmune diseases. An Ets family transcription factor, i.e., Spi-B (which is highly expressed in pDCs) is required for TLR7/9 signal-induced type I IFN production and can transactivate IFN-α promoter in synergy with IFN regulatory factor-7 (IRF-7). Herein, we analyzed how Spi-B contributes to the transactivation of the Ifna4 promoter. We performed deletion and/or mutational analyses of the Ifna4 promoter and an electrophoretic mobility shift assay (EMSA) and observed an Spi-B binding site in close proximity to the IRF-7 binding site. The EMSA results also showed that the binding of Spi-B to the double-stranded DNA probe potentiated the recruitment of IRF-7 to its binding site. We also observed that the association of Spi-B with transcriptional coactivator p300 was required for the Spi-B-induced synergistic enhancement of the Ifna4 promoter activity by Spi-B. These results clarify the molecular mechanism of action of Spi-B in the transcriptional activation of the Ifna4 promoter. • We have identified Spi-B binding site on the Ifna4 promoter. • Association of Spi-B with p300 was abolished in the S149A mutant of Spi-B. • Spi-B has a role in transactivation of the Ifna4 promoter by recruiting p300. [ABSTRACT FROM AUTHOR]