Positive regulation of the glucocorticoid receptor in human T-cells sensitive to the cytolytic effects of glucocorticoids.

L P Eisen,M S Elsasser,J M Harmon

doi:10.1016/s0021-9258(18)37890-6

L P Eisen, M S Elsasser + Show 1 more

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https://doi.org/10.1016/s0021-9258(18)37890-6

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Abstract

Regulation of glucocorticoid receptor (GR) protein and mRNA were examined in the human leukemic T-cell line CEM-C7. Unlike other cells in which GR regulation has been examined, the growth of these cells is inhibited by glucocorticoids, leading to cell death. Treatment of glucocorticoid-sensitive CEM-C7 cells with 1 microM dexamethasone for 18 h resulted in an increase in both cytoplasmic and nuclear GR protein, as determined by immunoblotting with anti-human GR antisera. Analysis of GR mRNA levels by Northern blotting revealed a corresponding increase in mRNA in steroid-treated cells. An increase in GR mRNA was detectable after as little as 3 h of treatment with dexamethasone, and GR mRNA concentration continued to increase for at least 18 h, well before the onset of growth arrest or cell death. GR mRNA concentration was not altered after dexamethasone treatment of the glucocorticoid-resistant mutant cell line ICR27TK.3, which lacks functional GR. Thus, the increase in GR seen in glucocorticoid-sensitive cells is a GR-mediated response. These results are in sharp contrast to the down-regulation of GR reported in other cells and tissues, and suggest that regulation of the GR by its cognate ligand may be tissue-specific.

Highlights

Regulation of glucocorticoid receptor (GR) protein cocorticoid sensitivity in mouse T-cells
Several lines of evidence indicate that intra- phase of the cell cycle and killed after exposure to glucocorcellular GR concentration is an important factor in determin- ticoids [16]
Gehring et al [1]have shown that there is a direct lation of the GR by its ligand plays a role in the response of relationship between endogenous GR concentration and glu- T-cells to glucocorticoids,we have investigated the regulation of the GR protein and its cognate mRNA in glucocorticoid

Summary

THEJOURNAOFLBIOLOGICAL CHEMISTRY

Vol 263, No 24, Issue of August 25, pp. 12044-12048, 1988 Printed in U.S.A. Positive Regulation ofthe Glucocorticoid Receptorin Human T-cells Sensitive to the Cytolytic Effects of Glucocorticoids*. Treatment of glucocorticoid-sensitive CEM-C7 cells tude of the transcriptional response from either a cotranswith 1 ~ L Mdexamethasone for 18 h resulted in an increase in both cytoplasmic and nuclear GR protein, as determined by immunoblotting with anti-human GR antisera. The costs of publication of this article were defrayed in part by the payment of page charges This trast to results reported for other tissues and systems, the amount of GR protein and mRNA in glucocorticoid-sensitive CEM-C7 cells increases significantly in response to steroid treatment. These resultssuggest that, in cells programmed to die after exposure to glucocorticoids, induction of GR may article must be hereby marked "advertisement" in accord- play an important role. The filter significant increase in GR mRNA afteraslittleas 3 h of was reprobed with a 32P-labeled S rRNA probe as described steroid treatment and that the concentration of GR mRNA by Forsthoefel and Thompson [29]

RESULTS

Glucocorticoid Receptor Induction

DISCUSSION

GlIuncdouccotritoicnoid Receptor

Methods