Phorbol ester modulates interleukin 6- and interleukin 1-regulated expression of acute phase plasma proteins in hepatoma cells
ISBN or ISSN
The Journal of biological chemistry
Publication Date / Copyright Date
American Society for Biochemistry and Molecular Biology
Interleukin 6 (IL 6) and interleukin 1 (IL-1) regulate the expression of acute phase plasma proteins in rat and human hepatoma cells. Phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), partially mimics the stimulatory effect of IL-6 but reduces that effect of IL-1. TPA and IL-6 act synergistically. These regulatory properties of TPA are also manifested in HepG2 cells transiently transfected with an indicator gene construct carrying the IL-1/IL-6 regulatory enhancer element of the rat alpha 1-acid glycoprotein gene. IL-6 and IL-1 act independently of TPA-inducible kinase C, and of changes in intracellular Ca2+ concentrations. However, prolonged pretreatment of HepG2 cells with TPA results in a drastically reduced cytokine response that is proportional to the loss of cell surface binding activity for the cytokine. These data suggest that hormones activating protein kinase C probably play a contributing role in stimulating the expression of acute phase plasma protein genes but they may be crucial in controlling the responsiveness of liver cells to inflammatory cytokines during subsequent stages of the hepatic acute phase reaction.
Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences
Acute-Phase Proteins, Animals, Carcinoma, Hepatocellular, Cell Line, Ethers, Humans, Interleukin-1, Interleukin-6, Interleukins, Ionomycin, Kinetics, Liver Neoplasms, Liver Neoplasms, Experimental, RNA, Messenger, Rats, Recombinant Proteins, Tetradecanoylphorbol Acetate, Transcription, Genetic
Baumann, H; Isseroff, H; Latimer, Jean Johanna; and Jahreis, G P., "Phorbol ester modulates interleukin 6- and interleukin 1-regulated expression of acute phase plasma proteins in hepatoma cells" (1988). College of Pharmacy Faculty Articles. 17.