Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity

Burnsides, Christopher; Corry, Jacqueline; Alexander, Jacob; Balint, Catherine; Cosmar, David; Phillips, Gary; Marketon, Jeanette I. Webster

doi:10.2147/jir.s33569

Cited by 10 publications

(14 citation statements)

References 56 publications

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“…Recently, Burnsides et al [839] have developed an ex vivo stimulation assay that determines the ability of leukocytes to upregulate anti-inflammatory genes such as GILZ and FKBP51 following exposure to dexamethasone. It is reasonable that a similar test may be developed to gene profiling lymphoid malignancies prior to and following GC treatment, where upregulation of the pro-apoptotic Bim gene would be a favorable predictor.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies

Sionov

2013

ISRN Hematology

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The initial response of lymphoid malignancies to glucocorticoids (GCs) is a critical parameter predicting successful treatment. Although being known as a strong inducer of apoptosis in lymphoid cells for almost a century, the signaling pathways regulating the susceptibility of the cells to GCs are only partly revealed. There is still a need to develop clinical tests that can predict the outcome of GC therapy. In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts. The journey through the multifaceted complexity of GC-induced apoptosis brings forth explanations for the differential treatment response and raises potential strategies for overcoming drug resistance.

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Section: Discussionmentioning

confidence: 99%

MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies

Sionov

2013

ISRN Hematology

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“…Basically, Dex is a kind of synthetic glucocorticoid which has an anti-inflammatory and immune-suppressive effects, then it could suppress the response of the immune system by inhibiting the secretion of pro-inflammatory cytokines such as TNFα and IL-6 [6,7]. Based on Galon et al (2002), glucocorticoid does not fully provide suppressive effects, but it could provide stimulant effects for several cells that associated with the immune system i.e.…”

Section: Dexamethasone Increase Population Number Of B Progenitor Celmentioning

confidence: 99%

Effect of Dexamethasone Administration toward Hematopoietic Stem Cells and Blood Progenitor Cells Expression on BALB/c Mice

Putra

Soewondo

Rifa’i

2015

J. Pure App. Chem. Res.

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Hematopoiesis plays important roles on maintaining body homeostasis. Dexamethasone (Dex) known as synthetic glucocorticoids and widely affect many regulations i.e. immune system, inflammation, reproduction and all aspects of metabolism. Generally Dex were used as therapeutic agents to ameliorate many kind of diseases including cancer and autoimmune diseases. The aims of this research were to investigate the effect of Dex administration toward expression of hema-topoietic stem cells and blood progenitor cells. Two weeks old BALB/c mice were used and treated with 3 groups of Dex administration i.e. untreated-mice, 0.5 mg/kg BW, and 10 mg/kg BW. Mice were sacrificed on day-7 after administration of Dex. The bone marrow stromal cells were isolated, and then followed by flow cytometry analysis. The result showed that, Dex administration with dose 0.5 mg/kg BW significantly increase the expression of hematopoietic stem cells, CD34 + , chemokines, SDF-1 + , erythroid progenitor cells, Gr-1-TER-119 + , granulocytes, Gr-1 + , and B progenitor cells, B220 + .

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“…Several methodologies have been investigated for determining cellular GC responsiveness in circulating human blood cells. 5 – 7 Vermeer et al 6 showed that GC-induced upregulation of the FK506 binding protein 5 ( FKBP5 ) in human leukocytes could be used as a marker of GC responsiveness. FKBP5 interacts with the glucocorticoid receptor (GR) and the subsequent GR-associated transcription machinery.…”

Section: Introductionmentioning

confidence: 99%

“… 8 Burnsides et al found similar upregulation in experiments using FKBP5 and the GC-induced leucine zipper ( GILZ ) gene, which is involved in the regulation of inflammation. 5 However, these assays have only been used in limited studies of altered GC responsiveness in clinical states that involve GC dysregulation 5 , 6 and the assays have not been evaluated in states of severe inflammation.…”

Section: Introductionmentioning

confidence: 99%

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An ex vivo RT-qPCR-based assay for human peripheral leukocyte responsiveness to glucocorticoids in surgically induced inflammation

Gråberg

Strömmer

Hedman

et al. 2015

JIR

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IntroductionAn assay to determine glucocorticoid (GC) responsiveness in humans could be used to monitor GC non-responsiveness in states of GC insufficiency and could provide a tool to adapt GC treatment to individual patients. We propose an ex vivo assay to test GC responsiveness in peripheral leukocytes. The assay was evaluated in a human experimental model of surgery-induced inflammation.Patients and methodsChanges in expression of the GC-regulated genes GILZ, IL1R2, FKBP5, and HLA-DR and glucocorticoid receptor alpha (GRα) were determined by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in peripheral leukocytes from surgical patients and healthy blood donors (total n=60) in response to low (1 nM) and high (1 µM) dexamethasone (DEX). The final selection of a suitable endogenous control gene was based on the studies of stability during DEX treatment and inflammation. Correlations between pre- and postoperative GC-induced gene expression, the postoperative systemic inflammatory and metabolic response (CRP, IL-6, white blood cell count, cytokines, resistin, free fatty acids, glucose, insulin, and adiponectin), and the clinical outcome were analyzed. The length of stay in the intensive care unit (ICU-LOS), the length of stay in the hospital, and postoperative complications were used to measure clinical outcome.ResultsWhen the blood donors were compared to the patients, there were no significant differences in the regulation of the genes in response to DEX, except for GRα. Preoperative, but not postoperative, gene regulation of GILZ and GRα was negatively correlated to ICU-LOS (P<0.05 and P<0.01, respectively). Preoperative GILZ and FKBP5 gene regulation was negatively correlated to postoperative systemic TNFα and MIP-1α levels.ConclusionWe suggest that this assay could be used to determine GC responsiveness. An alteration in preoperative GC responsiveness may be related to a patient’s ability to recover from surgically induced inflammatory stress.

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Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity

Cited by 10 publications

References 56 publications

MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies

MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies

Effect of Dexamethasone Administration toward Hematopoietic Stem Cells and Blood Progenitor Cells Expression on BALB/c Mice

An ex vivo RT-qPCR-based assay for human peripheral leukocyte responsiveness to glucocorticoids in surgically induced inflammation

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