Down-regulation of TNF-α receptors by conophylline in human T-cell leukemia cells
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- Published online on: November 1, 2003 https://doi.org/10.3892/ijo.23.5.1373
- Pages: 1373-1379
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Abstract
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.