INDUCTION OF METALLOTHIONEIN AND STOMATIN BY INTERLEUKIN-6 AND GLUCOCORTICOIDS IN A HUMAN AMNIOTIC CELL-LINE

Interleukin 6 (IL-6) is an important mediator of various kinds of infl ammatory 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 o f IL-6- and dexamethasone-treated cells was screened with cDNA probes from both induced and noninduced cells. Two cDNAs showed a differentia l 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 stomat ocytosis, absence of this protein in erythrocyte membranes is associat ed 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. and Casimir, C. M. (1992) Blood 79, 1593-1601]. In UAC cells both meta llothionein and stomatin are induced by dexamethasone and IL-6 in a mo re than additive manner. Western blot analysis shows that stomatin pro tein is induced in a similar way as its mRNA. IL-6 and dexamethasone i nduce a state of resistance against hydrogen peroxide toxicity in UAC cells. Metallothionein induction might be partly responsible for this cytoprotection against oxidative stress.