Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression.

TLDR

TNF is a monokine distinct from IL‑1 yet shares inflammatory effector functions characteristic of the host response to injury. The study examined whether recombinant human TNF regulates hepatic acute‑phase gene expression. At picomolar concentrations, TNF reversibly increased complement proteins factor B and C3 and alpha‑1 antichymotrypsin while decreasing albumin and transferrin in hepatoma cells, had no effect on C2, C4 or alpha‑1 proteinase inhibitor, increased factor B gene expression but not C2 in transfected fibroblasts, and acted pre‑translationally as shown by mRNA changes.

Abstract

The monokine, cachectin/tumor necrosis factor (TNF) differs from interleukin 1 (IL-1) in primary structure and in recognition by a distinct cellular receptor. It does, however, encode effector functions that are similar to those of IL-1 and characteristic of the host response to inflammation or tissue injury. Accordingly, we examined the possibility that recombinant-generated human TNF regulates hepatic acute-phase gene expression. In picomolar concentrations, TNF mediated reversible, dose- and time-dependent increases in biosynthesis of complement proteins factor B and C3, alpha 1 antichymotrypsin, and decreases in biosynthesis of albumin and transferrin in human hepatoma cell lines (Hep G2, Hep 3B). Biosynthesis of complement proteins C2 and C4, and alpha 1 proteinase inhibitor were not affected by TNF. TNF also increased factor B gene expression, but had no effect on C2 gene expression, in murine fibroblasts transfected with cosmid DNA bearing the human C2 and factor B genes. The effect of TNF on acute-phase protein expression (C3, factor B, albumin) was pre-translational as shown by changes in specific messenger RNA content.