Induction of metallothionein in astrocytes by cytokines and heavy metals

Biol Signals. 1994 May-Jun;3(3):157-68. doi: 10.1159/000109539.

Abstract

Immunohistochemical staining of human and rat brains for metallothionein (MT) using a monoclonal anti-MT antibody (MT45) revealed that protoplasmic astrocytes, which are densely localized in the gray matter, contain high levels of MT. Human U373MG astrocytoma cells were stimulated with interleukin (IL)-1 or heavy metals to produce MT. When expression of MT in U373MG cells was analyzed by Northern blotting or indirect immunofluorescence using the MT45 antibody, it was found that IL-1 (> or = 10 U/ml), CdCl2 (50 microM) and high concentrations of ZnCl2 (500 microM) induced marked biosynthesis of MT.IL-6 (up to 3,000 U/ml) and lower concentrations of ZnCl2 (10-50 microM), however, showed little inducing activity. Hippocampal astrocytes in primary culture produced a relatively high basal level of MT. The MT level increased in response to addition of IL-1 (> or = 10 U/ml), ZnCl2 (50 microM) and CdCl2 (5 microM). However, the increase induced by IL-6 (1,000 U/ml) was not very marked. The in vivo induction of MT in the brain by cytokines is not fully understood. However, our data and other indirect evidence suggest that IL-1 may be a potent stimulator of MT induction in astrocytes. Furthermore, the astrocytoma cell line, U373MG, is a suitable in vitro system to analyze the expression of MT in astrocytes.

Publication types

  • Review

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Brain / physiology
  • Cadmium / pharmacology
  • Cadmium Chloride
  • Cells, Cultured
  • Chlorides / pharmacology
  • Humans
  • Immunohistochemistry
  • Interleukin-1 / pharmacology
  • Metallothionein / biosynthesis*
  • Metallothionein / physiology
  • Rats
  • Signal Transduction
  • Zinc Compounds / pharmacology

Substances

  • Chlorides
  • Interleukin-1
  • Zinc Compounds
  • Cadmium
  • zinc chloride
  • Metallothionein
  • Cadmium Chloride