Induction of metallothionein and stomatin by interleukin‐6 and glucocorticoids in a human amniotic cell line

Abstract

Interleukin 6 (IL‐6) is an important mediator of various kinds of inflammatory and immune responses. The human amniotic cell line UAC has an increased number of IL‐6 receptors after treatment by glucocorticoids. To find a possible activity of IL‐6 on these cells, a cDNA library of IL‐6‐ and dexamethasone‐treated cells was screened with cDNA probes from both induced and non‐induced cells. Two cDNAs showed a differential hybridization signal. The first one corresponds to metallothionein, a group of small cysteine‐rich proteins thought to participate in the metabolism and storage of zinc and to protect cells against oxidative damage. A second cDNA corresponds to the recently cloned cDNA of band 7 integral membrane protein also called stomatin. In hereditary stomatocytosis, absence of this protein in erythrocyte membranes is associated with high Na+ and low K+ intracellular concentrations [Stewart, G. W., Hepworth‐Jones, B. E., Keen, J. N., Dash, B. C. J., Argent, A. C. & Casimir, C. M. (1992) Blood 79, 1593–1601]. In UAC cells both metallothionein and stomatin are induced by dexamethasone and IL‐6 in a more than additive manner. Western blot analysis shows that stomatin protein is induced in a similar way as its mRNA. IL‐6 and dexamethasone induce a state of resistance against hydrogen peroxide toxicity in UAC cells. Metallothionein induction might be partly responsible for this cytoprotection against oxidative stress. Copyright © 1994, Wiley Blackwell. All rights reserved