Tumor Necrosis Factor-α Production by Human Hepatoma Cell Lines Is Resistant to Drugs That Are Inhibitory to Macrophages

Publisher Website
Google Scholar
Abstract
Little is known about the potential of immunomodulatory agents to lower tumor necrosis factor-α(TNF-α) synthesis in tissues of nonmonocytic origin. We studied effects of diverse drugs on the formation of immunoreactive TNF-α in the human hepatoma cell lines HepG2 and Hep3B, in which TNF-α production was induced by treatment (3 h incubation periods) with interleukin-1β (IL-1β, 300 pg/ml) or phorbol myristate acetate (PMA, 100 nmol/l). TNF-α production in IL-1β-stimulated or PMA-stimulated hepatocyte cultures was not altered following the addition of dihydrocortisone (≤ 1 μg/ml), dibutyryl-cAMP (db-cAMP,≤ 100 μmol/1), adenosine (≤ 1 mmol/l), thalidomide (≤ 25 μg/ml), or cyclosporine (≤ 300 ng/ml). TNF-α production was inhibited by taurolidine (≥300 μg/ml), but this inhibition was associated with reduced cell viability. Pentoxifylline (1 mg/ml) did not influence PMA-induced TNF-α production, but it augmented IL-1β-induced TNF-α production. Measurements of TNF-α mRNA by RT-PCR indicated that pentoxifylline exerted its effect posttranscriptionally. Additional studies with PMA-treated human whole blood cultures confirmed that pentoxifylline, db-cAMP, and adenosine reduced TNF-α production by leukocytes. These results provide first evidence to assume cell type-specific effects of immunomodulatory drugs on TFN-α synthesis, which may be relevant with respect to their clinical application.

This publication has 29 references indexed in Scilit: