Induction of Th1-type cytokines by lipoteichoic acid-related preparation isolated from OK-432, a penicillin-killed streptococcal agent |
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Authors: | Okamoto M Ohe G Oshikawa T Nishikawa H Furuichi S Yoshida H Matsuno T Saito M Sato M |
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Affiliation: | Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, 3-18-15 Kuramoto-cho, 7708504, Tokushima, Japan. |
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Abstract: | 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. |
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