Molecular mechanisms involved in the estrogen-dependent regulation of calcineurin in systemic lupus erythematosus T cells
Copyright 2000 Academic Press.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 95(2000), 2 vom: 01. Mai, Seite 124-34 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , |
| Format: | Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2000
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Estrogens RNA, Messenger Receptors, Estrogen Estradiol 4TI98Z838E Calcineurin EC 3.1.3.16 |
| Zusammenfassung: | Copyright 2000 Academic Press. Previous experiments in our laboratory indicated that calcineurin expression and PP2B phosphatase activity increased when estrogen was cultured with SLE T cells but not with T cells from normal women. In this report we extended our findings to show that estrogen receptor (ER) antagonism by ICI 182,780 inhibited the estrogen-dependent increase in calcineurin mRNA and phosphatase PP2B activity indicating that estrogen action was mediated through the ER. Inhibition of de novo protein synthesis with cycloheximide suggested that the estrogen-dependent increase in T cell calcineurin mRNA was a direct effect of the ER and new protein synthesis was not required. Estrogen increased calcineurin mRNA in systemic lupus erythematosus (SLE) T cells at 6 h after the start of culture correlating with increased phosphatase activity at this same time. Phosphatase activity increased significantly (P < 0.02) in lupus T cells cultured for 8 h in estradiol-containing medium. Reverse transcription and polymerase chain amplification revealed that ER-beta and ER-alpha were expressed in female and male T cells from SLE patients and normal controls. However, calcineurin steady-state mRNA levels were unaffected by estradiol in cultured T cells from male SLE patients and normal male and female controls. These data indicate that estrogen, bound to the ER, evokes a direct increase in calcineurin expression in T cells from female lupus patients. This gender-specific response suggests that ER function is altered in women with the female predominant autoimmune disease, SLE |
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| Beschreibung: | Date Completed 16.06.2000 Date Revised 21.11.2013 published: Print Citation Status MEDLINE |
| ISSN: | 1521-7035 |