Glucocorticoid receptor translational isoforms underlie maturational stage-specific glucocorticoid sensitivities of dendritic cells in mice and humans
| Autor: | Christine M. Jewell, Nick Z. Lu, Ingrid K. Bender, John A. Cidlowski, Yun Cao, Soon Cheon Shin, Athanasios K. Konstantinidis, Robert P. Schleimer |
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| Rok vydání: | 2013 |
| Předmět: |
Gene isoform
medicine.medical_specialty Cellular differentiation Immunology Drug Resistance chemical and pharmacologic phenomena Inflammation Biology Biochemistry Substrate Specificity Mice Receptors Glucocorticoid Glucocorticoid receptor Glucocorticoid Sensitivity Internal medicine medicine Animals Humans Protein Isoforms Glucocorticoids Cells Cultured Immunobiology Mice Inbred BALB C Caspase 3 Cell Differentiation hemic and immune systems Dendritic Cells Cell Biology Hematology Hematopoietic Stem Cells In vitro Cell biology Endocrinology Protein Biosynthesis Female Ectopic expression medicine.symptom hormones hormone substitutes and hormone antagonists Glucocorticoid medicine.drug |
| Zdroj: | Blood. 121:1553-1562 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Although glucocorticoids are a profoundly important class of anti-inflammatory and immunosuppressive agents, their actions in dendritic cells (DCs) are not well understood. We found that dexamethasone, a potent glucocorticoid, selectively induced apoptosis in mature, but not in immature, DCs in healthy mice, in mice with experimental airway inflammation, and in vitro in bone marrow–derived DCs. Distinct glucocorticoid receptor (GR) translational isoforms expressed in immature and mature DCs probably contribute to the DC maturational stage-specific glucocorticoid sensitivity. The GR-D isoforms were the predominant isoforms in immature DCs, whereas the proapoptotic GR-A isoform was the main isoform in mature DCs. Ectopic expression of the GR-A isoform in immature DCs increased glucocorticoid sensitivity and RU486, a selective GR antagonist, inhibited the glucocorticoid sensitivity of mature DCs. Furthermore, the distinct expression pattern of GR isoforms in immature and mature murine DCs was also observed in human monocyte–derived DCs. These studies suggest that glucocorticoids may spare immature DCs and suppress mature DCs and inflammation via differential expression of GR translational isoforms. |
| Databáze: | OpenAIRE |
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