Activation of human dendritic cells by an effective component of OK-432, a streptococcal agent, mediated by toll-like receptor 4.

DOI 2 Citations 25 References
  • OKAMOTO Masato
    Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry
  • FURUICHI Sachiko
    Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry
  • OH-E Go
    Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry
  • NISHIKAWA Hidetomo
    Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry
  • TANO Tomoyuki
    Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry
  • YOSHIDA Hideo
    Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry
  • SATO Mitsunobu
    Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry

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  • ＯＫ‐４３２有効成分によるＴｏｌｌ‐Ｌｉｋｅ　Ｒｅｃｅｐｔｏｒ　４を介した樹状細胞活性化

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Abstract

We have reported that a lipoteichoic acid-related molecule (OK-PSA) isolated from OK-432, a penicillin killedstreptococcal preparation, is an effective inducer of Thl-type cytokines, and elicits anti-tumor activity in tumor-bearing mice. Dendritic cells (DCs) are potent antigen-presenting cells that promote immune responses against tumor cells. It is important to induce matu rationof DCs to enhance their anti-tumor activity. In the current study, we examined the effect of OK-PSA in the maturation of DCs. OK-PSA treatment of immature DCs induced from human periph eralblood monocytes increased the surface expression of major histocompatibility complex class II, CD80, CD83 and CD86 most effectively among the other stimuli such as OK-432, lipopolysaccharide and tumor necrosis factor-α. Further, OK-PSA-activated DCs enhanced the proliferation of allogeneic T cells and induced allospecific cytotoxic T lymphocytes (CTL) as well as interferon-γ-producing cells far better than the original OK-432. Maturation of DCs induced by OK-PSA was almost completely inhibited by the addition of the antibody against toll-like receptor (TLR) 4, a member of the toll-like receptor family that has been implicated in bacterial component inducedcell signaling. OK-PSA also matured DCs derived from oral cancer patients that were express ingboth TLR4 and MD-2 genes, while OK-PSA stimulated DCs derived from patients in which the expression of MD-2 mRNA was only faint, did not induce CTL activity. These findings indicate that OK-PSA induces maturation of human DCs in vitro mediated by TLR4/MD-2 signaling. OK-PSA may be a potent adjuvant for DC-based immunotherapy for patients with malignant diseases.

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