Promoter-mediated, dexamethasone-induced increase in cystatin C production by HeLa cells
Abstract
Cystatin C, an efficient inhibitor of cysteine proteinases, is present in all investigated human extracellular fluids. Dexamethasone caused a significant and dose-dependent increase in the cystatin C secretion of cultivated HeLa cells up to a maximal increase of 80% at 10(-6) mol l-1 dexamethasone. Increased production of cystatin C was also observed at lower concentrations, suggesting that glucocorticoids might play a physiological role in the production of cystatin C. The effect of dexamethasone on the cystatin C gene expression was also studied in a transient transfection expression system using chimeric plasmid constructs of the cystatin C gene promoter (positions -2 to -1084) coupled to the structural gene for human growth hormone (hGH). In this system, a small, but statistically significant, increase in hGH secretion was also observed upon dexamethasone treatment, suggesting that the glucocorticoid-induced increase in secretion of cystatin C is due to a promoter-mediated increase in transcription of the cystatin C gene.
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The positive association between GC exposure and CyC production has been recapitulated experimentally in vitro, in vivo, and in patients.
“This positive association between GC exposure and CyC production has been recapitulated experimentally in vitro,18 in vivo,19 and in patients.11,20,21”
From Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy (2023) · cites this paper as [18]
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Warfel, A. H., Zucker-Franklin, D., Frangione, B., & Ghiso, J. (1987) · The Journal of experimental medicine · doi:10.1084/jem.166.6.1912 · Cited by 126 · see citing works
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Involvement of cystatin C in pathophysiology of CNS diseases
Nagai, A. (2008) · Frontiers in Bioscience · doi:10.2741/2941 · Cited by 44 · see citing works
Kleeman, S. O., Thakir, T. M., Demestichas, B., Mourikis, N., Loiero, D., Ferrer, M., Bankier, S., Riazat-Kesh, Y. J. R. A., Lee, H., Chantzichristos, D., et al. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100347 · Cited by 37 · see citing works
- Authors
- Bjarnadóttir, M., Grubb, A., & Ólafsson, Í.
- Affiliations
- Skåne University Hospital (SE)
- Venue
- Scandinavian Journal of Clinical and Laboratory Investigation
- Publisher
- Informa UK Limited
- Published
- 1995-01
- Volume
- 55
- Issue
- 7
- Pages
- 617-623
- ISSN
- 0036-5513 (ISSN-L)
- 1502-7686
- OpenAlex
- W2153764627
- Cited by
- 157
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 9 · 2017: 4 · 2016: 3 · 2015: 7 · 2014: 9 · 2013: 4 · 2012: 8
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Scandinavian Journal of Clinical and Laboratory Investigation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- cystatin C, dexamethasone, glucocorticoids, HeLa cells, gene transcription, protein secretion, cysteine protease inhibitors, growth hormone secretion, transient transfection
- MeSH terms
- Dexamethasone, Dose-Response Relationship, Drug, Gene Expression Regulation, Glucocorticoids, HeLa Cells, Humans, Promoter Regions, Genetic, Growth Hormone, Time Factors, Transcription, Genetic, Transfection, Cysteine Proteinase Inhibitors, Cystatins, Cystatin C
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