Intracellular cAMP regulates the cytotoxicity of recombinant tumor necrosis factor for L cells in vitro.
Tumor necrosis factor (TNF) destroys certain tumor cells in vitro. Using the classical TNF-sensitive cell line L929 and its resistant derivative, we show here that the sensitivity of cells to TNF depends in large measure on the intracellular cAMP concentration. An experimental increase of the intra-cellular cAMP concentration can substantially enhance the sensitivity of L-cells to TNF. This increase in TNF sensitivity is seen only in TNF-sensitive cells but not in TNF-resistant cells. An increase in intracellular cAMP levels has been obtained by adding cell permeable dibutyryl cAMP to the culture medium or by culturing L929 cells in the presence of reagents which cause the elevation of intracellular cAMP concentrations.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology*; D004351:Drug Resistance; D006023:Glycoproteins / Q000633:toxicity*; D007739:L Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D011458:Prostaglandins E / Q000494:pharmacology; D011994:Recombinant Proteins / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D011458:Prostaglandins E; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP