A study on the immunomodulation of polysaccharopeptide through the TLR4-TIRAP/MAL-MyD88 signaling pathway in PBMCs from breast cancer patients

Immunopharmacol Immunotoxicol. 2013 Aug;35(4):497-504. doi: 10.3109/08923973.2013.805764. Epub 2013 Jun 27.

Abstract

Context: Polysaccharopeptide (PSP), isolated from the Coriolus versicolor COV-1 strain, has been widely used as an immunoadjuvant for cancer immunotherapy.

Objective: The present study was undertaken to examine the role of PSP on the TLR4-TIRAP/MAL-MyD88 signaling pathway in peripheral blood mononuclear cells (PBMCs) from breast cancer patients.

Methods: For blockade of TLR4, cells were cultured with or without PSP and anti-TLR4 for 24 h, and then the mRNA and proteins (IL-12, IL-6, and TNF-α) levels in each group were detected by Q-PCR and ELISA. Meanwhile, Q-PCR and western blot analysis were used to detect the expression of TLR4-TIRAP/MAL-MyD88 pathway genes and proteins under the regulation of PSP.

Results: As anticipated, the transcription and expression of genes (IL-12 and TNF-α) in the anti-TLR4 group were significantly downregulated compared with the control group, while genes (IL-12, IL-6 and TNF-α) in the PSP group were significantly upregulated. Moreover, the mRNA levels in the PSP+anti-TLR4 group were significantly upregulated compared with the anti-TLR4 group. The results of ELISA were as the same as Q-PCR. Genes, kinase phosphorylation levels and proteins in the TLR4 pathway were significantly upregulated by PSP.

Conclusions: Collectively, our study revealed that PSP has an immunoregulatory effect through regulation of the TLR4-TIRAP/MAL-MyD88 signaling pathway.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology*
  • Breast Neoplasms
  • Cytokines / immunology
  • Female
  • Humans
  • Immunomodulation / drug effects*
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / pathology
  • Membrane Glycoproteins / immunology*
  • Myeloid Differentiation Factor 88 / immunology*
  • Proteoglycans / chemistry
  • Proteoglycans / pharmacology*
  • RNA, Messenger / immunology
  • Receptors, Interleukin-1 / immunology*
  • Signal Transduction / drug effects*
  • Signal Transduction / immunology
  • Toll-Like Receptor 4 / immunology*
  • Trametes / chemistry*

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • MYD88 protein, human
  • Membrane Glycoproteins
  • Myeloid Differentiation Factor 88
  • Proteoglycans
  • RNA, Messenger
  • Receptors, Interleukin-1
  • TIRAP protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • polysaccharide peptide