Th1-cytokine induction and anti-tumor effect of 55 kDa protein isolated from Aeginetia indica L., a parasitic plant
Autor: | Mitsunobu Sato, Tomoyuki Tano, Hideo Yoshida, Kayo Uyama, Hidetomo Nishikawa, Go Ohe, Toru Sakai, Takashi Bando, Sachiko Furuichi, Masato Okamoto, Shinya Ohkubo, Tetsuya Oshikawa, Kunisuke Himeno |
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Rok vydání: | 2001 |
Předmět: |
Cancer Research
Cellular immunity medicine.drug_class medicine.medical_treatment Fibrosarcoma Immunology Mice Nude Aeginetia indica Biology Monoclonal antibody Antibodies Mice Th2 Cells Interferon medicine Tumor Cells Cultured Immunology and Allergy Animals Humans Cells Cultured Plant Proteins Mice Inbred BALB C Interleukin Neoplasms Experimental Th1 Cells biology.organism_classification Cytotoxicity Tests Immunologic Molecular biology Antineoplastic Agents Phytogenic Survival Rate Cytokine Oncology biology.protein Cytokines Tumor necrosis factor alpha Female Antibody Spleen medicine.drug |
Zdroj: | Cancer immunology, immunotherapy : CII. 50(5) |
ISSN: | 0340-7004 |
Popis: | We have isolated a 55 kDa protein from the seed extract of Aeginetia indica L. (AIL), a parasitic plant, by affinity chromatography on an N-hydroxysuccinimide-activated Sepharose High Performance column bound with F3, a monoclonal antibody that neutralizes the cytokine-inducing and anti-tumor effect of AIL. In the present study, we examined this protein (AILb-A) for cytokine induction and anti-tumor effects by animal study, using syngeneic Meth-A tumor-bearing BALB/c mice, in which the Th2 response is genetically dominant. AILb-A administration resulted in markedly increased levels of Th1 cytokines [interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-12 and IL-18] in the sera derived from Meth-A-bearing mice. The in vitro re-stimulation with AILb-A of splenocytes derived from AILb-A-primed mice also selectively induced Th1-type cytokines and antigen-specific killer cell activity. The neutralizing test using cytokine-specific antibodies revealed that AILb-A-induced IL-18 plays a most significant role for and killer cell-inducing activities. Furthermore, IL-12 and IL-18 induced by AILb-A inhibited specifically IL-10 and IL-4 production, respectively. Finally, we examined the anti-tumor effect of AILb-A in both Meth-A-bearing BALB/c mice and Meth-A-bearing nude mice with BALB/c background. AILb-A exhibited a striking anti-tumor effect in normal BALB/c mice inoculated with Meth-A cells. In athymic nude mice, the anti-tumor effect of AILb-A was relatively weak. These findings strongly suggested that AILb-A is a potent Th1 inducer and may be a useful immunotherapeutic agent for patients with malignant diseases. |
Databáze: | OpenAIRE |
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