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Molecular mechanisms involved in the estrogen-dependent regulation of calcineurin in systemic lupus erythematosus T cells.
Clin Immunol 2000; 95(2):124-34CI

Abstract

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.

Authors+Show Affiliations

Division of Molecular Biology and Biochemistry, School of Biological Sciences, Kansas City, Missouri 64110, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10779406

Citation

Rider, V, et al. "Molecular Mechanisms Involved in the Estrogen-dependent Regulation of Calcineurin in Systemic Lupus Erythematosus T Cells." Clinical Immunology (Orlando, Fla.), vol. 95, no. 2, 2000, pp. 124-34.
Rider V, Jones SR, Evans M, et al. Molecular mechanisms involved in the estrogen-dependent regulation of calcineurin in systemic lupus erythematosus T cells. Clin Immunol. 2000;95(2):124-34.
Rider, V., Jones, S. R., Evans, M., & Abdou, N. I. (2000). Molecular mechanisms involved in the estrogen-dependent regulation of calcineurin in systemic lupus erythematosus T cells. Clinical Immunology (Orlando, Fla.), 95(2), pp. 124-34.
Rider V, et al. Molecular Mechanisms Involved in the Estrogen-dependent Regulation of Calcineurin in Systemic Lupus Erythematosus T Cells. Clin Immunol. 2000;95(2):124-34. PubMed PMID: 10779406.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular mechanisms involved in the estrogen-dependent regulation of calcineurin in systemic lupus erythematosus T cells. AU - Rider,V, AU - Jones,S R, AU - Evans,M, AU - Abdou,N I, PY - 2000/4/26/pubmed PY - 2000/6/24/medline PY - 2000/4/26/entrez SP - 124 EP - 34 JF - Clinical immunology (Orlando, Fla.) JO - Clin. Immunol. VL - 95 IS - 2 N2 - 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. SN - 1521-6616 UR - https://www.unboundmedicine.com/medline/citation/10779406/Molecular_mechanisms_involved_in_the_estrogen_dependent_regulation_of_calcineurin_in_systemic_lupus_erythematosus_T_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1521-6616(00)94844-7 DB - PRIME DP - Unbound Medicine ER -