title: [Analysis of the immuno-activation mechanism of OK-432--phagocytosis, release of active components and TLR4 signaling].
abstract: Although we have reported that Toll-like receptor (TLR) 4 is involved in OK-432-induced anti-cancer immunity, its detailed mechanism remained uncertain. We hypothesized that OK-432 may first be captured, dissolved by phagocytes, and then active components released from the cells may stimulate TLR4. This hypothesis was examined by the current in vitro experiments. We used TS-2 MoAb which recognizes OK-PSA, an active component of OK-432. First, we observed that OK-432-induced cytokine production by dendritic cells (DCs) and macrophages was significantly inhibited by cytochalasin B, a phagocytosis inhibitor. Immunofluorescence staining by using TS-2 clearly demonstrated that OK-432 was captured and dissolved by these cells. OK-PSA was detected in the supernatants derived from OK-432-treated DC culture by ELISA with TS-2. The supernatants from OK-432-treated DC culture, but not from untreated DC culture, increased NF-kappaB activity in TLR4-expressing cells. The increased NF-kappaB activity was inhibited by TS-2. These findings elucidated the mechanism mediated by phagocytosis and TLR4 signaling in the OK-432 action.
authors.affiliation: Second Dept. of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tano
authors.forename: Masato
authors.initials: M
authors.lastname: Okamoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oshikawa
authors.forename: Sharif Uddin
authors.initials: SU
authors.lastname: Ahmed
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Sato
mesh_terms: D000818:Animals; D003571:Cytochalasin B / Q000494:pharmacology; D003713:Dendritic Cells / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D017737:Macrophages, Peritoneal / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D009369:Neoplasms / Q000276:immunology*; D010587:Phagocytosis / Q000502:physiology*; D010844:Picibanil / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D010844:Picibanil; D003571:Cytochalasin B