title: Polysaccharopeptide exerts immunoregulatory effects via MyD88-dependent signaling pathway.
abstract: OBJECTIVE
  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.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, PR China.
authors.forename: Zifang
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, PR China.
authors.forename: Zhixue
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400010, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, PR China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, PR China. Electronic address: yixibao111@163.com.
authors.forename: Yixi
authors.initials: Y
authors.lastname: Bao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology*; D056747:Immunomodulation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D011509:Proteoglycans / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D007155:Immunologic Factors; D053594:Myeloid Differentiation Factor 88; D011509:Proteoglycans; D051197:Toll-Like Receptor 4; C093216:polysaccharide peptide
keywords: Anti-tumor; MyD88-dependent; Polysaccharopeptide