1,4-β-d-Glucomannan from Dendrobium officinale Activates NF-кB via TLR4 to Regulate the Immune Response

Abstract

2,3-O-acetylated-1,4-β-d-glucomannan (DOP-1-1) is a polysaccharide isolated from the stem of Dendrobium officinale. DOP-1-1 has been demonstrated to have remarkable immunomodulatory properties, but little is known about the influence of its structural diversity on bioactivity (and even less about the exact mechanism underlying its immune responses). First, DOP-1-1 was stabilized at different temperatures and pH conditions based on differential scanning calorimetry and size exclusion-chromatography–high-performance liquid chromatography. Then, a detailed study on the effects of DOP-1-1 on a human leukemia monocytic cell line (THP-1) under normal conditions was undertaken. DOP-1-1 promoted the translocation of nuclear factor-kappa B (NF-κB) and degradation of IκB proteins. The expression of genes and proteins closely associated with the immune, survival and apoptotic functions of NF-κB were analyzed by quantitative real-time RT-PCR. Furthermore, CCL4 and IP10 were confirmed to be the novel targets of the immune response stimulated by DOP-1-1. The phosphorylation of NF-кB was inhibited by treatment with a toll-like receptor 4 (TLR4) antagonist (TAK-242) and myeloid differentiation factor 88 (MyD88) inhibitor (ST2825). These data suggested: (i) the O-acetylated glucomannan DOP-1-1 is present in the steady state in low-pH solutions; (ii) DOP-1-1 can induce an immune response through NF-кB mediated by a TLR4 signaling pathway; and (iii) CCL4 and IP10 could be the novel targets of the immune response stimulated by O-acetylated glucomannan.

Synthesis and Cytotoxicity Studies of Wood-Based Cationic Cellulose Nanocrystals as Potential Immunomodulators

“…Polysaccharides, such as 2,3-O-acetylated-1,4-β-D-glucomannan, have been shown to have immunomodulatory properties, including the stimulation of cytokines, interleukin 1-beta (IL-1β), and tumor necrosis alpha (TNF-α) in human cell lines [1,2]. The immune system is a complex network of different cell types and mediators responsible for the defense of an organism against pathogens as well as the maintenance of tolerance to innocuous antigens [3].…”

Redox DAPK1 destabilizes Pellino1 to govern inflammation-coupling tubular damage during septic AKI

“…ST2825 is a selective MyD88 homodimerization inhibitor that attenuates pro-inflammatory cytokine production in human monocytic cells and protects mice against ischemia/reperfusion (I/R) injuries 37 - 39 . Considering the potential therapeutic capacity based on DAPK1 deactivation or ablation in CLP mice, we hypothesized that management of septic AKI might further benefit from the combination therapy with DAPK1-i and ST2825.…”

Genome-wide identification of Cellulose-like synthase D gene family in Dendrobium catenatum

“…The CslM lineage was widely distributed in eudicots, and the CslJ clade, which is also capable of directing (1,3;1,4)-β-glucan biosynthesis, is widely distributed in monocots [12]. Cellulose synthase-like D (CslD) gene was predicted to be located on the Golgi membrane and catalyzes the synthesis of 1,4-β-D-glucomannan from GDP glucose and GDP mannose (Figure 1) [23,24]. It is conserved in all land plants, and among the ten Csl subfamilies, it shows the highest sequence similarity to the cellulose synthase genes, suggesting that it plays fundamental roles in plant development [25,26].…”