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Down-regulation of TNF-α receptors by conophylline in human T-cell leukemia cells

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In the course of our screening for tumor necrosis factor-α (TNF-α) function inhibitors, conophylline, a vinca alkaloid isolated from the plant Ervatamia microphylla, was found to inhibit TNF-α-induced NF-κB activation. We studied the effect of conophylline on TNF-α-induced NF-κB and JNK activations in human T-cell leukemia Jurkat cells. Conophylline inhibited both of these TNF-α-induced activations. It also inhibited phosphorylation and degradation of I-κB-α. Moreover, a receptor binding assay using [125I]-TNF-α showed that this inhibitory effect was due to a decrease in the binding of TNF-α to the cells. Scatchard analysis of the binding data indicated that conophylline induced only a small change in the affinity of the receptors but a significant change in the receptor number. FACS analysis showed that conophylline reduced the expression of CD120a/TNFR1, the high-affinity receptor for TNF-α, on the cell surface. On the other hand, conophylline did not affect the kinetics of internalization and degradation of TNF-α/receptor complexes or the half-life of TNF-α binding sites. These results indicate that conophylline down-regulates the expression of the TNF-α receptors on the cell surface.
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Document Type: Research Article

Affiliations: Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan

Publication date: November 1, 2003

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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