Expression of the glucocorticoid receptor from the 1A promoter correlates with T lymphocyte sensitivity to glucocorticoid-induced cell death
Open accessAbstract
Glucocorticoid (GC) hormones cause pronounced T cell apoptosis, particularly in immature thymic T cells. This is possibly due to tissue-specific regulation of the glucocorticoid receptor (GR) gene. In mice the GR gene is transcribed from five separate promoters designated: 1A, 1B, 1C, 1D, and 1E. Nearly all cells express GR from promoters 1B–1E, but the activity of the 1A promoter has only been reported in the whole thymus or lymphocyte cell lines. To directly assess the role of GR promoter use in sensitivity to glucocorticoid-induced cell death, we have compared the activity of the GR 1A promoter with GC sensitivity in different mouse lymphocyte populations. We report that GR 1A promoter activity is restricted to thymocyte and peripheral lymphocyte populations and the cortex of the brain. The relative level of expression of the 1A promoter to the 1B–1E promoters within a lymphocyte population was found to directly correlate with susceptibility to GC-induced cell death, with the extremely GC-sensitive CD4+CD8+ thymocytes having the highest levels of GR 1A promoter activity, and the relatively GC-resistant αβTCR+CD24int/low thymocytes and peripheral T cells having the lowest levels. DNA sequencing of the mouse GR 1A promoter revealed a putative glucocorticoid-response element. Furthermore, GR 1A promoter use and GR protein levels were increased by GC treatment in thymocytes, but not in splenocytes. These data suggest that tissue-specific differences in GR promoter use determine T cell sensitivity to glucocorticoid-induced cell death.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Glucocorticoids reduce circulating T cells by enhancing their migration to bone marrow and secondary lymphoid organs and trigger T cell apoptosis through up-regulation of BIM.
“In contrast to neutrophils, GCs reduce the levels of circulating T cells by enhancing their migration back to the bone-marrow and secondary lymphoid organs (47, 48). GCs also trigger T cells apoptosis, notably through the up-regulation of BIM (49, 50).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [50]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Sapolsky, R. M., Romero, L. M., & Munck, A. U. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.1.0389 · Cited by 7,541 · see citing works
Primary structure and expression of a functional human glucocorticoid receptor cDNA
Hollenberg, S. M., Weinberger, C., Ong, E. S., Cerelli, G., Oro, A. E., Lebo, R. V., Thompson, E. B., Rosenfeld, M. G., & Evans, R. M. (1985) · Nature · doi:10.1038/318635a0 · Cited by 1,871 · see citing works
DNA binding of the glucocorticoid receptor is not essential for survival
Reichardt, H. M., Kaestner, K. H., Tuckermann, J., Kretz, O., Wessely, O., Bock, R., Gass, P., Schmid, W., Herrlich, P., Angel, P., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81183-6 · Cited by 1,068 · see citing works
Karin, M., Haslinger, A., Holtgreve, H., Richards, R. I., Krauter, P., Westphal, H. M., & Beato, M. (1984) · Nature · doi:10.1038/308513a0 · Cited by 907 · see citing works
Wellman, C. L. (2001) · Journal of Neurobiology · doi:10.1002/neu.1079 · Cited by 594 · see citing works
Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPAR?2
Lecka‐Czernik, B., Gubrij, I. B., Moerman, E. J., Kajkenova, O., Lipschitz, D. A., Manolagas, S. C., & Jilka, R. L. (1999) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(19990901)74:3 · Cited by 403 · see citing works
Intracellular Receptor Concentration Limits Glucocorticoid-Dependent Enhancer Activity*
Vanderbilt, J. N., Miesfeld, R. L., Maler, B. A., & Yamamoto, K. R. (1987) · Molecular Endocrinology · doi:10.1210/mend-1-1-68 · Cited by 349 · see citing works
Zacharchuk, C., Merćep, M., Chakraborti, P. K., Simons, S. S., & Ashwell, J. D. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.145.12.4037 · Cited by 309 · see citing works
The Glucocorticoid Receptor: Coding a Diversity of Proteins and Responses through a Single Gene
Yudt, M. R., & Cidlowski, J. A. (2002) · Molecular Endocrinology · doi:10.1210/me.2002-0106 · Cited by 273 · see citing works
Webster, J. C., Jewell, C. M., Bodwell, J. E., Munck, A., Sar, M., & Cidlowski, J. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.14.9287 · Cited by 261 · see citing works
McCormick, J. A., Lyons, V., Jacobson, M. D., Noble, J., Diorio, J. C., Nyirenda, M., Weaver, S., Ester, W. A., Yau, J. L. W., Meaney, M. J., et al. (2000) · Molecular Endocrinology · doi:10.1210/mend.14.4.0438 · Cited by 258 · see citing works
Blomgren, H., & Andersson, B. (1970) · Cellular Immunology · doi:10.1016/0008-8749(70)90041-9 · Cited by 245 · see citing works
Tissue-specific regulation of glucocorticoid receptor mRNA by dexamethasone.
Kalinyak, J. E., Dorin, R. I., Hoffman, A. R., & Perlman, A. J. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)60980-9 · Cited by 228 · see citing works
Iwata, M., Hanaoka, S., & Sato, K. (1991) · European Journal of Immunology · doi:10.1002/eji.1830210316 · Cited by 199 · see citing works
Structural Determinants of a Glucocorticoid Receptor Recognition Element
Nordeen, S. K., Suh‐Burgmann, E., Kühnel, B., & Hutchison, C. A. (1990) · Molecular Endocrinology · doi:10.1210/mend-4-12-1866 · Cited by 198 · see citing works
Lymphocytes : a practical approach
Klaus, G. G. B. (1987) · IRL Press eBooks · Cited by 173 · see citing works
Flouriot, G., Griffin, C., Kenealy, M.-R., Sonntag-Buck, V., & Gannon, F. (1998) · Molecular Endocrinology · doi:10.1210/mend.12.12.0209 · Cited by 165 · see citing works
Multiple Promoters Exist in the Human GR Gene, One of Which Is Activated by Glucocorticoids
Breslin, M. B., Geng, C.-D., & Vedeckis, W. V. (2001) · Molecular Endocrinology · doi:10.1210/mend.15.8.0696 · Cited by 157 · see citing works
Autoregulation of glucocorticoid receptor gene expression
Burnstein, K. L., Bellingham, D. L., Jewell, C. M., Powell-Oliver, F. E., & Cidlowski, J. A. (1991) · Steroids · doi:10.1016/0039-128x(91)90124-e · Cited by 152 · see citing works
T-cell glucocorticoid receptor is required to suppress COX-2-mediated lethal immune activation
Brewer, J. A., Khor, B., Vogt, S. K., Muglia, L. M., Fujiwara, H., Haegele, K. E., Sleckman, B. P., & Muglia, L. J. (2003) · Nature Medicine · doi:10.1038/nm895 · Cited by 149 · see citing works
At least three promoters direct expression of the mouse glucocorticoid receptor gene.
Strähle, U., Schmidt, A., Kelsey, G., Stewart, A. F., Cole, T. J., Schmid, W., & Schütz, G. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.15.6731 · Cited by 132 · see citing works
Self-citationSeveral Different Cell Surface Molecules Control Negative Selection of Medullary Thymocytes
Kishimoto, H., & Sprent, J. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.1.65 · Cited by 126 · see citing works
Human glucocorticoid receptor cDNA contains sequences sufficient for receptor down-regulation.
Burnstein, K. L., Jewell, C. M., & Cidlowski, J. A. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39112-4 · Cited by 124 · see citing works
Ramdas, J., Liu, W., & Harmon, J. M. (1999) · PubMed · Cited by 106 · see citing works
Crosstalk pathway for inhibition of glucocorticoid-induced apoptosis by T cell receptor signaling
Jamieson, C. A. M., & Yamamoto, K. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.13.7319 · Cited by 104 · see citing works
Burnstein, K. L., Jewell, C. M., Sar, M., & Cidlowski, J. A. (1994) · Molecular Endocrinology · doi:10.1210/mend.8.12.7708063 · Cited by 102 · see citing works
Eisen, L. P., Elsasser, M. S., & Harmon, J. M. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)37890-6 · Cited by 97 · see citing works
Characterization of the Human Glucocorticoid Receptor Promoter
Nobukuni, Y., Smith, C. L., Hager, G. L., & Detera‐Wadleigh, S. D. (1995) · Biochemistry · doi:10.1021/bi00025a028 · Cited by 78 · see citing works
The further redefining of steroid-mediated signaling
Hammes, S. R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0530224100 · Cited by 74 · see citing works
Pedersen, K. B., & Vedeckis, W. V. (2003) · Biochemistry · doi:10.1021/bi034651u · Cited by 64 · see citing works
Tamada, K., Harada, M., Abe, K., Li, T., & Nomoto, K. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.3.1239 · Cited by 63 · see citing works
Characterization of promoter 1B in the human glucocorticoid receptor gene
Nunez, B. S., & Vedeckis, W. V. (2002) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(01)00676-1 · Cited by 56 · see citing works
Brewer, J. A., Sleckman, B. P., Swat, W., & Muglia, L. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.3.1309 · Cited by 55 · see citing works
Stress-free T-cell development: glucocorticoids are not obligatory
Godfrey, D. I., Purton, J. F., Boyd, R. L., & Cole, T. J. (2000) · Immunology Today · doi:10.1016/s0167-5699(00)01741-2 · Cited by 50 · see citing works
Self-citationDifferential autoregulation of glucocorticoid receptor expression in human T- and B-cell lines
Denton, R., Eisen, L. P., Elsasser, M. S., & Harmon, J. M. (1993) · Endocrinology · doi:10.1210/endo.133.1.8319574 · Cited by 49 · see citing works
Barrett, T. J., Vig, E., & Vedeckis, W. V. (1996) · Biochemistry · doi:10.1021/bi960058j · Cited by 40 · see citing works
Human glucocorticoid receptor gene promotor—homologous down regulation
Govindan, M. V., Pothier, F., Leclerc, S., Palaniswami, R., & Xie, B. (1991) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(91)90197-d · Cited by 36 · see citing works
Takeda, K., & Dennert, G. (1994) · Transplantation · doi:10.1097/00007890-199408270-00017 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Coutinho, A. E., & Chapman, K. E. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.04.005 · Cited by 1,815 · see citing works
The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain
Bellavance, M.-A., & Rivest, S. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00136 · Cited by 419 · see citing works
- Authors
- Purton, J. F., Monk, J. A., Liddicoat, D. R., Kyparissoudis, K., Sakkal, S., Richardson, S. J., Godfrey, D. I., & Cole, T. J.
- Affiliations
- The University of Melbourne (AU)
- Monash University (AU)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-09
- Volume
- 173
- Issue
- 6
- Pages
- 3816-3824
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2168469696
- Cited by
- 79
- References
- 41
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 3 · 2012: 7
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Figshare (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- glucocorticoid receptor, glucocorticoid-induced cell death, T cell apoptosis, thymocytes, CD4+CD8+ thymocytes, glucocorticoid response element, tissue-specific gene expression, splenocytes, thymus cortex, glucocorticoid sensitivity
- MeSH terms
- Animals, Base Sequence, Cell Differentiation, Cell Survival, Cells, Cultured, Cerebral Cortex, Dexamethasone, Dose-Response Relationship, Immunologic, Glucocorticoids, Molecular Sequence Data, Organ Specificity, Promoter Regions, Genetic, Receptors, Glucocorticoid, RNA, Messenger, Spleen, T-Lymphocytes, Up-Regulation, Cell Death, Sequence Analysis, DNA, Response Elements, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
