Title

Phorbol ester modulates interleukin 6- and interleukin 1-regulated expression of acute phase plasma proteins in hepatoma cells

ISBN or ISSN

0021-9258

Publication Title

The Journal of biological chemistry

Volume

263

Issue

33

Publication Date / Copyright Date

11-25-1988

First Page

17390

Last Page

17396

Publisher

American Society for Biochemistry and Molecular Biology

Abstract

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.

Disciplines

Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences

Keywords

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