Effects of retinoic acid (vitamin A) on tumor necrosis factor cytolytic action.
Tumor necrosis factor (TNF) is a monokine produced primarily by macrophages. TNF has a number of activities including direct lysis of certain transformed cells and induction of antiviral activity. One of the protoypical transformed cell lines used for studying TNF cytolysis is murine L-929 cells. Because of the lysis, TNF has not been shown to have antiviral activity in these cells. Since retinoic acid (RA) induces a normal phenotype in the L-929 cells, we sought to determine if their conversion to a normal phenotype would 1) render them insensitive to the cytolytic effect and 2) allow for the development of an antiviral state. We present evidence that both the cis- and trans- forms of RA and to a lesser extent, the RA precursor beta-carotene, can inhibit recombinant human TNF cytolytic activity in mouse L-929 cells. However, blockage of the cytolytic activity does not allow development of an antiviral state.
Hughes
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TK
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77550.
Fulep
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D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D007700:Kinetics; D007739:L Cells; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects; D019207:beta Carotene
D000998:Antiviral Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019207:beta Carotene; D002338:Carotenoids; D014212:Tretinoin