Mechanisms of Macrophage Immunomodulatory Activity Induced by a New Polysaccharide Isolated From Polyporus umbellatus (Pers.) Fries

Abstract

Bladder cancer is one of the most malignant tumors closely associated with macrophage immune dysfunction. The Chinese medicine polyporus has shown excellent efficacy in treating bladder cancer, with minimal side effects. However, its material basis and mechanism of action remain unclear. A new water-soluble polysaccharide (HPP) with strong immunomodulatory activity was isolated from the fungus Polyporus umbellatus (Pers.) Fries. HPP had an average molecular weight of 6.88 kDa and was composed mainly of an <-(1→ 4)-linked D-galactan backbone. The immunomodulatory activity of HPP was determined in vitro, and the results revealed that it could obviously increase the secretion of immune factors by IFN-γ-stimulated macrophages, including nitric oxide (NO), interleukin-6 (IL-6), interleukin-1β (IL-1β), RANTES and interleukin-23 (IL-23), and the expression of the cell membrane molecule CD80. In addition, HPP was recognized by Toll-like receptor 2 (TLR2) and activated the signaling pathways of NF-κB and NLRP3 in a bladder cancer microenvironment model, indicating that HPP could enhance host immune system function. These findings demonstrated that HPP may be a potential immune modulator in the treatment of immunological diseases or bladder cancer therapy.

Immune-Enhancing Effects of a Novel Glucan from Purple Sweet Potato Ipomoea batatas (L.) Lam on RAW264.7 Macrophage Cells via TLR2- and TLR4-Mediated Pathways

“…28 The induction of TLR expressions is one of the molecular mechanisms for the polysaccharides' immune-enhancing effect. 29 Therefore, we aimed to ascertain the regulatory effect of PSPP-1 on the expressions of TLR2 and TLR4 on RAW264.7 cells by western blot. RAW264.7 is a mouse macrophage cell line with abundant expression of TLR on the cell membrane and is a good model for the study of the TLR-mediated signaling pathway.…”

“…PRRs have been reported to participate in signal transmission of macrophages, and TLRs play a key role in innate immune responses to enhance the defense system . The induction of TLR expressions is one of the molecular mechanisms for the polysaccharides’ immune-enhancing effect . Therefore, we aimed to ascertain the regulatory effect of PSPP-1 on the expressions of TLR2 and TLR4 on RAW264.7 cells by western blot.…”

Homogeneous Polyporus Polysaccharide Inhibit Bladder Cancer by Resetting Tumor-Associated Macrophages Toward M1 Through NF-κB/NLRP3 Signaling

“…However, whether HPP promotes the polarization of TAMs toward the M1 phenotype trough NF-κB remains unclear. Activated macrophages can secrete NO, which plays an important role in antitumor cells and microorganisms ( 20 , 32 ). Here, we demonstrated that HPP dose-dependently upregulated the secretion of pro-inflammatory factors such as IL-6, TNF-α, NO, MIP-1α and MIP-1β as well as NO in macrophages trough NF-κB in TME.…”

“…The new polysaccharide was first isolated from polyporus total polysaccharide using Sephadex G-100 gel-filtration column (2.9 × 50cm), which was proven to have an α-(1→ 4)-linked D-galactan backbone ( 20 ).…”

Structural Characterization and Anticoagulant Activity of a 3-O-Methylated Heteroglycan From Fruiting Bodies of Pleurotus placentodes

“…The bands at 1,147, 1,076, and 1,030 cm −1 were attributed to the stretching vibration of pyran ring (Dong et al, 2016). In addition, the bands at 874 cm −1 were β-glycosidic bands, and the bands at 805 cm −1 were α-glycosidic bands (Azmi et al, 2012;Liu et al, 2020), indicating that PPp-W contained an αand β-pyranose ring.…”