Polysaccharopeptide exerts immunoregulatory effects via MyD88-dependent signaling pathway

• Published in: International journal of biological macromolecules 2016-01, Vol.82, p.201-207
• Main Authors: Feng, Zifang, Wang, Zhixue, Yang, Min, Zhou, Lijing, Bao, Yixi
• Format: Article
• Language: English
• Subjects: Animals; Anti-tumor; Antineoplastic Agents - pharmacology; Carcinoma, Ehrlich Tumor - drug therapy; Carcinoma, Ehrlich Tumor - immunology; Carcinoma, Ehrlich Tumor - metabolism; Carcinoma, Ehrlich Tumor - pathology; Cell Line, Tumor; Cytokines - metabolism; Cytotoxicity, Immunologic - drug effects; Disease Models, Animal; Female; Immunologic Factors - pharmacology; Immunomodulation - drug effects; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Mice; MyD88-dependent; Myeloid Differentiation Factor 88 - metabolism; Polysaccharopeptide; Proteoglycans - pharmacology; Signal Transduction - drug effects; Spleen - drug effects; Spleen - immunology; Spleen - metabolism; Thymus Gland - drug effects; Thymus Gland - immunology; Thymus Gland - metabolism; Toll-Like Receptor 4 - metabolism; Tumor Burden - drug effects
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2015.11.002

The present study is to investigate the immunomodulatory mechanism and related pathways of polysaccharopeptide (PSP) in mice bearing Ehrlich's ascites carcinoma (EAC). 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. 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. PSP plays an immunoregulatory effect through MyD88-dependent signaling pathway.