Induction of Th1-type cytokines by lipoteichoic acid-related preparation isolated from OK-432, a penicillin-killed streptococcal agent.
We have isolated the lipoteichoic acid (LTA)-related molecule (OK-PSA) from OK-432, a streptococcal preparation, by an affinity chromatography on CNBr-activated Sepharose 4B-bound TS-2 monoclonal antibody (mAb) that neutralizes interferon (IFN)-gamma-inducing activity of OK-432. In in vitro experiments using human peripheral blood mononuclear cells (PBMC), OK-PSA induced IFN-gamma, interleukin (IL)-2, IL-12, IL-18, tumor necrosis factor (TNF)-alpha and TNF-beta that are generally called "Th1-type cytokines" both in protein and in mRNA levels. Furthermore, the neutralizing test using cytokine-specific antibodies demonstrated that IL-18 plays a most significant role for IFN-gamma- and killer cell-inducing ability of OK-PSA among the other cytokines tested. These findings clearly indicated that OK-PSA, an LTA-related molecule, is a main effective component of OK-432, and is a potent inducer of Th1-type cytokines by T cell and natural killer (NK) cell activation mediated by monocytes-derived IL-18, and that it may be a useful immunotherapeutic agent for the patients with malignancies better than original OK-432.
Okamoto
M
M
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, 3-18-15 Kuramoto-cho, 7708504, Tokushima, Japan.
Ohe
G
G
Oshikawa
T
T
Nishikawa
H
H
Furuichi
S
S
Yoshida
H
H
Matsuno
T
T
Saito
M
M
Sato
M
M
D000818:Animals; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000302:isolation & purification / Q000494:pharmacology; D002352:Carrier Proteins / Q000302:isolation & purification / Q000494:pharmacology; D020170:Caspase 1 / Q000378:metabolism / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000378:metabolism; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010406:Penicillins / Q000494:pharmacology*; D010844:Picibanil / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013297:Streptococcus pyogenes / Q000276:immunology*; D013682:Teichoic Acids / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D016207:Cytokines; D020382:Interleukin-18; D008070:Lipopolysaccharides; D010406:Penicillins; D012333:RNA, Messenger; D013682:Teichoic Acids; C014689:streptococcal M protein; D016753:Interleukin-10; D010844:Picibanil; C009900:lipoteichoic acid; D007371:Interferon-gamma; D020170:Caspase 1