Polysaccharopeptide exerts immunoregulatory effects via MyD88-dependent signaling pathway.

Abstract

AIMS:

The present study is to investigate the immunomodulatory mechanism and related pathways of polysaccharopeptide (PSP) in mice bearing Ehrlich's ascites carcinoma (EAC).

METHODS:

Twelve female wild-type C57 mice were randomly divided into three groups. Another twelve female myeloid differentiation factor 88 (MyD88)-deficient mice were randomly assigned to three groups. Cell survival and peritoneal macrophage phagocytosis were measured using WST8 assay. Nitric oxide concentration was determined by Griess reaction. ELISA was used to measure tumor necrosis factor-α and interferon-γ levels. Quantitative real-time PCR was employed to measure mRNA levels. Western blotting was performed to determine protein expression.

RESULTS:

PSP significantly inhibited the proliferation of EAC cells via macrophage activation. PSP-primed macrophages exhibited a higher tumoricidal activity than untreated macrophages. PSP markedly inhibited the growth of the tumor and increased macrophage phagocytosis, nitric oxide release and cytokine secretion. Expression of MyD88 was markedly increased in PSP-treated groups, while ST2825 inhibited MyD88 signaling and interfered with nitric oxide release and the secretion of tumor necrosis factor-α and interferon-γ. Moreover, mRNA and protein levels associated with MyD88-dependent signaling pathway in MyD88-deficient mice group were significantly down-regulated compared with wild-type mice group.

CONCLUSIONS:

PSP plays an immunoregulatory effect through MyD88-dependent signaling pathway.

• Authors: Zifang Feng, Zhixue Wang, Min Yang, Lijing Zhou, Yixi Bao
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 82 Pg. 201-7 (Jan 2016) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 26546866 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cytokines
• Immunologic Factors
• Myeloid Differentiation Factor 88
• Proteoglycans
• Toll-Like Receptor 4
• polysaccharide peptide

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Carcinoma, Ehrlich Tumor (drug therapy, immunology, metabolism, pathology)
• Cell Line, Tumor
• Cytokines (metabolism)
• Cytotoxicity, Immunologic (drug effects)
• Disease Models, Animal
• Female
• Immunologic Factors (pharmacology)
• Immunomodulation (drug effects)
• Macrophages (drug effects, immunology, metabolism)
• Mice
• Myeloid Differentiation Factor 88 (metabolism)
• Proteoglycans (pharmacology)
• Signal Transduction (drug effects)
• Spleen (drug effects, immunology, metabolism)
• Thymus Gland (drug effects, immunology, metabolism)
• Toll-Like Receptor 4 (metabolism)
• Tumor Burden (drug effects)