Inducer-Specific Bidirectional Regulation by Thalidomide and Phenylphthalimides of Tumor Necrosis Factor-α Production☆
1996
Abstract Regulation by thalidomide [ N (α)-phthalimidoglutarimide] of tumor necrosis factor (TNF)-α production was found to be inducer-specific. Thalidomide enhances TNF-α production by human leukemia HL-60 cells induced with 12- O -tetradecanoylphorbol 13-acetate (TPA), while it inhibits TNF-α production induced with okadaic acid (OA) in the same cell line. Some phthalimide analogs, including PP-33 [2-(2,6-diisopropylphenyl)-1 H -isoindole-1,3-dione] and its 4,5,6,7-tetrafluoro derivative (FPP-33), also showed such an inducer-specific bidirectional TNF-α production-regulating activity. The structure–activity relationships of the compounds tested are similar, but not identical, in the TPA-stimulated HL-60 and OA-stimulated HL-60 assay systems.
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