Inhibitory Effects of Inonotus obliquus Polysaccharide on Inflammatory Response in Toxoplasma gondii-Infected RAW264.7 Macrophages.

Rui Sang,Chunting Li,Xuemei Zhang,Meng Wang,Kexin Yan,Wei Wang,Bingjie Ge,Hongyuan Zhou,Xin Zhao,Haitao Li,Angelica Oliveira Gomes

doi:10.1155/2021/2245496

Abstract

Our previous reports have shown that Inonotus obliquus polysaccharide (IOP) has protective effects against Toxoplasma gondii (T. gondii) infection in vivo. The aim of the present research is to explore the in vitro anti-inflammatory effects of IOP and its mechanism in RAW264.7 macrophages infected by T. gondii. In this study, it is indicated that IOP decreased the excessive secretion of inflammatory cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-4, and IL-6 in T. gondii-infected RAW264.7 macrophages. IOP effectively suppressed the mRNA expression of these cytokines and chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α). Moreover, IOP inhibited the phosphorylation of inhibitor kappa B kinase α/β (IKKα/β), inhibitor κBα (IκBα), p65 in nuclear factor-kappa B (NF-κB) signaling pathway and p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2) in mitogen-activated protein kinases (MAPKs) signaling pathway. Meantime, IOP prevented NF-κB p65 and c-Jun translocation from the cytoplasm to the nucleus. Further, IOP downregulated the protein expression of toll-like receptor 2 (TLR2) and TLR4 in T. gondii-infected RAW264.7 macrophages. The above results suggest that IOP can inhibit the inflammatory response infected with T. gondii via regulating TLR2/TLR4-NF-κB/MAPKs pathways and exerting its anti-T. gondii role in vitro.

Highlights

Toxoplasma gondii (T. gondii), as an apicomplexan parasitic organism in warm-blooded animals and humans [1], can infect almost all nucleated cells [2]
Effect of Inonotus obliquus polysaccharide (IOP) on Cytokine Contents in RAW264.7 Macrophages Infected by T. gondii. e MTT method was used to detect the cytotoxicity of IOP on RAW264.7 cells to determine the safe doses of IOP
Our data revealed that IOP inhibited the inflammatory response caused by T. gondii infection in RAW264.7 macrophages by suppressing inflammatory cytokines and chemokines

Summary

Introduction

Toxoplasma gondii (T. gondii), as an apicomplexan parasitic organism in warm-blooded animals and humans [1], can infect almost all nucleated cells [2]. When the host’s immune function is low or defective, T. gondii proliferates in vivo and results in systemic inflammatory responses and multiple organ damage [6,7,8]. Erefore, the inflammatory response is an important link in host resistance to T. gondii and an important cause of host pathological damage. TLRs can recognize the glycerophosphoinositide- (GPI-) anchored protein on the surface of T. gondii and activate the downstream nuclear factor-κappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways, the activation of signaling pathways further stimulates multiple immune

Methods

Results

Conclusion