The glucocorticoid receptor 1A3 promoter correlates with high sensitivity to glucocorticoid-induced apoptosis in human lymphocytes

Douglas R Liddicoat; Konstantinos Kyparissoudis; Stuart P Berzins; Timothy J Cole; Dale I Godfrey

Journal article

The glucocorticoid receptor 1A3 promoter correlates with high sensitivity to glucocorticoid-induced apoptosis in human lymphocytes

Douglas R Liddicoat, Konstantinos Kyparissoudis, Stuart P Berzins, Timothy J Cole, Dale I Godfrey

IMMUNOLOGY AND CELL BIOLOGY | WILEY | Published : 2014

DOI: 10.1038/icb.2014.57

Abstract

Glucocorticoids (GCs) are powerful inhibitors of inflammation and immunity. Although glucocorticoid-induced cell death (GICD) is an important part of GCs actions, the cell types and molecular mechanisms involved are not well understood. Untranslated exon 1A3 of the human glucocorticoid receptor (GR) gene is a major determinant of GICD in GICD-sensitive human cancer cell lines, operating to dynamically upregulate GR levels in response to GCs. We measured the GICD sensitivity of freshly isolated peripheral blood mononuclear cells and thymocytes to dexamethasone in vitro, relating this to GR exon 1A3 expression. A clear GICD sensitivity hierarchy was detected: B cells>thymocytes/natural killer ..

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University of Melbourne Researchers

Dale Godfrey Author Microbiology and Immunology

Stuart Berzins Author Microbiology and Immunology

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Funding Acknowledgements

We thank Daniel Pellicci and Mark Veitch for technical assistance. We are grateful to David Ritchie, Royal Melbourne Hospital, for critically appraising this manuscript. We also thank the Picchi Brothers Foundation for generously supporting our flow cytometry facility and Ken Field for assisting with FAGS sorting. This work was supported by a National Health and Medical Research Council of Australia (NHMRC) Project Grant (350302). We also acknowledge the following support: DEL, Monash University Graduate Scholarship; DIG, NHMRC Senior Principal Research Fellowship (1020770); NHMRC Program Grants (454569 and 1013667); SPB, NHMRC project grant (454363) and RD Wright Fellowship (454731).