Understanding the response of dendritic cells to activation by streptococcal preparation OK-432

Anticancer Res. 2005 Nov-Dec;25(6B):4231-8.

Abstract

Background: The streptococcal preparation OK-432 induces maturation of T cells and dendritic cells (DCs). However, the mechanisms by which OK-432 induces DC maturation are not well understood.

Materials and methods: The effects of OK-432 and TNF-alpha on peripheral blood mononuclear cells (PBMCs) were compared. Antibody-based approaches were used to detect proteins characteristic of antigen-presenting cells and cytokines. Cytotoxicity was evaluated by measuring the release of LDH after incubation of effector and target cells. The TLR-4 levels were measured by real-time quantitative PCR.

Results: Changes in cell surface marker levels were detected in both treatment groups but OK-432 had a greater effect on induction of Th-1-type cytokines. Furthermore, TLR-4 mRNA was up-regulated in cells from two out of five patients in response to OK-432, but not in response to TNF-alpha.

Conclusion: OK-432 has a more profound effect on human DCs than TNF-alpha and may act through multiple signaling pathways.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology*
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Picibanil / immunology
  • Picibanil / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Toll-Like Receptor 4 / biosynthesis
  • Toll-Like Receptor 4 / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation

Substances

  • Cytokines
  • RNA, Messenger
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Picibanil