title: A study on immunomodulatory mechanism of Polysaccharopeptide mediated by TLR4 signaling pathway.
abstract: BACKGROUND
  Polysaccharopeptide (PSP), isolated from Coriolus versicolor COV-1 strain, is a protein-bound polysaccharide widely used as immunoadjuvant for cancer immunotherapy. Although the immunomodulatory activity of PSP has been well established, the precise molecule mechanisms of its biological activity have yet to be fully elucidated.
  
  
  METHODS
  In the present study, we first investigated the immunomodulatory activity of PSP in peritoneal macrophages from C57BL/10J (TLR4(+/+)) and C57BL/10ScCr (TLR4(-/-)) mice carrying a defective toll-like receptor-4 (TLR4) gene and then evaluated PSP for its effect on tumor inhibition rates and the immune organ index in above two different strains of mice. In addition, PSP were also evaluated for its activation of TLR4, TLR4-downstream molecules (TRAF6, NF-κB and AP-1) in spleens of tumor-bearing C57BL/10J (TLR4(+/+)) and C57BL/10ScCr (TLR4(-/-)) mice.
  
  
  RESULTS
  The results showed that PSP had adjuvant activities in stimulating expressions of cytokines as well as TLR4, TRAF6, phosphorylation of NF-κB p65 transcription factors and phosphorylation of c-Jun (a component of the transcription factor AP-1) in peritoneal macrophages from C57BL/10J (TLR4(+/+)) mice but not from C57BL/10ScCr (TLR4(-/-)) mice. In vivo PSP as well as Adriamycin (ADM) decreased the mean weights of tumors compared with normal saline and PSP increased thymus index and spleen index relative to ADM in tumor-bearing C57BL/10J (TLR4(+/+)) mice but not in C57BL/10ScCr (TLR4(-/-)) mice.
  
  
  CONCLUSIONS
  We demonstrated that PSP activates peritoneal macrophages in vitro via TLR4 signaling pathway and PSP functions its immunoregulatory effect in vivo also via TLR4 signaling pathway. These data strongly suggest TLR4 signaling pathway is involved in PSP-mediated immunomodulatory activities.
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Lin Jiang Rd. #76, Yuzhong District, 400010, Chongqing, China. cqwangzhixue@163.com.
authors.forename: Zhixue
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Lin Jiang Rd. #76, Yuzhong District, 400010, Chongqing, China. wan7908116@163.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Dong
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Lin Jiang Rd. #76, Yuzhong District, 400010, Chongqing, China. fengzifang4744@126.com.
authors.forename: Zifang
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Lin Jiang Rd. #76, Yuzhong District, 400010, Chongqing, China. yushuang_6251161@163.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Lin Jiang Rd. #76, Yuzhong District, 400010, Chongqing, China. yixibao@163.com.
authors.forename: Yixi
authors.initials: Y
authors.lastname: Bao
mesh_terms: D000818:Animals; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D007155:Immunologic Factors; D015850:Interleukin-6; D016328:NF-kappa B; D011509:Proteoglycans; D048029:TNF Receptor-Associated Factor 6; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C093216:polysaccharide peptide