Regulation of Synthesis and Secretion of Major Rat Acute-Phase Proteins by Recombinant Human interleukin-6 (BSF-2/IL-6) in Hepatocyte Primary Cultures

Eur J Biochem. 1988 Apr 15;173(2):287-93. doi: 10.1111/j.1432-1033.1988.tb13997.x.

Abstract

The regulation of the three major acute-phase proteins alpha 2-macroglobulin, cysteine proteinase inhibitor and alpha 1-antitrypsin by recombinant human interleukin-1 beta, recombinant human interleukin-6 and recombinant human tumor necrosis factor alpha was studied in rat hepatocyte primary cultures. Synthesis and secretion of the acute-phase proteins was measured after labeling with [35S]methionine and immunoprecipitation. Incubation of hepatocytes with interleukin-6 led to dose-dependent and time-dependent changes in the synthesis of the three major acute-phase proteins and albumin, similar to those occurring in vivo during experimental inflammation. alpha 2-Macroglobulin and cysteine proteinase inhibitor synthesis was induced 54-fold and 8-fold, respectively, 24 h after the addition of 100 units/ml interleukin-6. At the same time synthesis of the negative acute-phase protein albumin was reduced to 30% of controls. Half-maximal effects were achieved with 4 units interleukin-6/ml. Interleukin-1 beta had only a partial effect on the regulation of the four patients studied: only a twofold stimulation of alpha 2-macroglobulin and a 60% reduction of albumin synthesis were observed. Tumor necrosis factor alpha did not alter the synthesis of acute-phase proteins. The stimulation of alpha 2-macroglobulin and cysteine proteinase inhibitor synthesis by interleukin-6 was inhibited by interleukin-1 beta in a dose-dependent manner. In pulse-chase experiments the effect of interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha on the secretion of acute-phase proteins was examined. Interleukin-6 markedly accelerated the secretion of total proteins and alpha 2-macroglobulin, whereas the secretion of cysteine proteinase inhibitor, alpha 1-antitrypsin and albumin was not affected. The inhibition of N-glycosylation by tunicamycin abolished the effect of interleukin-6 on the secretion of alpha 2-macroglobulin, indicating a possible role of interleukin-6 on N-glycosylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / biosynthesis
  • Acute-Phase Proteins / metabolism*
  • Animals
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Humans
  • Interleukin-6
  • Interleukins / pharmacology*
  • Liver / metabolism*
  • Proteins / pharmacology*
  • Rats
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Acute-Phase Proteins
  • Interleukin-6
  • Interleukins
  • Proteins
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha