Glucocorticoid receptor and signal transduction pathway associated with immune cell activation

2013 ◽  
Vol 221 ◽  
pp. S32
Author(s):  
Marco Racchi ◽  
Antonella Pinto ◽  
Cristina Lanni ◽  
Emanuela Corsini
Keyword(s):  
Signal Transduction ◽  
Glucocorticoid Receptor ◽  
Cell Activation ◽  
Immune Cell ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Immune Cell Activation

scholarly journals A Genetic Analysis of Glucocorticoid Receptor Signaling: Identification and Characterization of Ligand-Effect Modulators in Saccharomyces cerevisiae

Genetics ◽  
2000 ◽  
Vol 156 (3) ◽  
pp. 963-972
Author(s):  
Raquel Sitcheran ◽  
Roger Emter ◽  
Anastasia Kralli ◽  
Keith R Yamamoto
Keyword(s):  
Signal Transduction ◽  
Glucocorticoid Receptor ◽  
Cellular Response ◽  
Transmembrane Protein ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Ligand Effect ◽  
Yeast Genetic ◽  
Identification And Characterization

Abstract To find novel components in the glucocorticoid signal transduction pathway, we performed a yeast genetic screen to identify ligand-effect modulators (LEMs), proteins that modulate the cellular response to hormone. We isolated several mutants that conferred increased glucocorticoid receptor (GR) activity in response to dexamethasone and analyzed two of them in detail. These studies identify two genes, LEM3 and LEM4, which correspond to YNL323w and ERG6, respectively. LEM3 is a putative transmembrane protein of unknown function, and ERG6 is a methyltransferase in the ergosterol biosynthetic pathway. Analysis of null mutants indicates that LEM3 and ERG6 act at different steps in the GR signal transduction pathway.

scholarly journals Androgen Receptor Pathway Activity Assay for Sepsis Diagnosis and Prediction of Favorable Prognosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Wilbert Bouwman ◽  
Wim Verhaegh ◽  
Anja van de Stolpe
Keyword(s):  
Signal Transduction ◽  
Bacterial Infection ◽  
Immune Cell ◽  
Signal Transduction Pathway ◽  
Diagnostic Assay ◽  
Transduction Pathway ◽  
Activity Assay ◽  
Pathway Activity ◽  
Sepsis Diagnosis ◽  
Favorable Prognosis

Introduction: Sepsis is a life-threatening complication of a bacterial infection. It is hard to predict which patients with a bacterial infection will develop sepsis, and accurate and timely diagnosis as well as assessment of prognosis is difficult. Aside from antibiotics-based treatment of the causative infection and supportive measures, treatment options have remained limited. Better understanding of the immuno-pathophysiology of sepsis is expected to lead to improved diagnostic and therapeutic solutions.Functional activity of the innate (inflammatory) and adaptive immune response is controlled by a dedicated set of cellular signal transduction pathways, that are active in the various immune cell types. To develop an immune response-based diagnostic assay for sepsis and provide novel therapeutic targets, signal transduction pathway activities have been analyzed in whole blood samples from patients with sepsis.Methods: A validated and previously published set of signal transduction pathway (STP) assays, enabling determination of immune cell function, was used to analyze public Affymetrix expression microarray data from clinical studies containing data from pediatric and adult patients with sepsis. STP assays enable quantitative measurement of STP activity on individual patient sample data, and were used to calculate activity of androgen receptor (AR), estrogen receptor (ER), JAK-STAT1/2, JAK-STAT3, Notch, Hedgehog, TGFβ, FOXO-PI3K, MAPK-AP1, and NFκB signal transduction pathways.Results: Activity of AR and TGFβ pathways was increased in children and adults with sepsis. Using the mean plus two standard deviations of normal pathway activity (in healthy individuals) as threshold for abnormal STP activity, diagnostic assay parameters were determined. For diagnosis of pediatric sepsis, the AR pathway assay showed high sensitivity (77%) and specificity (97%), with a positive prediction value (PPV) of 99% and negative prediction value (NPV) of 50%. For prediction of favorable prognosis (survival), PPV was 95%, NPV was 21%. The TGFβ pathway activity assay performed slightly less for diagnosing sepsis, with a sensitivity of 64% and specificity of 98% (PPV 99%, NPV 39%).Conclusion: The AR and TGFβ pathways have an immunosuppressive role, suggesting a causal relation between increased pathway activity and sepsis immunopathology. STP assays have been converted to qPCR assays for further evaluation of clinical utility for sepsis diagnosis and prediction of prognosis, as well as for prediction of risk at developing sepsis in patients with a bacterial infection. STPs may present novel therapeutic targets in sepsis.

scholarly journals CD28 and T cell antigen receptor signal transduction coordinately regulate interleukin 2 gene expression in response to superantigen stimulation.

1992 ◽  
Vol 175 (4) ◽  
pp. 1131-1134 ◽  
Author(s):  
J D Fraser ◽  
M E Newton ◽  
A Weiss
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Cell Antigen

Activation of an immune response requires intercellular contact between T lymphocytes and antigen-presenting cells (APC). Interaction of the T cell antigen receptor (TCR) with antigen in the context of major histocompatibility molecules mediates signal transduction, but T cell activation appears to require the induction of a second costimulatory signal transduction pathway. Recent studies suggest that interaction of CD28 with B7 on APC might deliver such a costimulatory signal. To investigate the role of CD28 signal transduction during APC-dependent T cell activation, we have used Staphylococcal enterotoxins (SEs) presented by a B7-positive APC. We used anti-B7 monoclonal antibodies and a mutant interleukin 2 (IL-2) promoter construct, unresponsive to CD28-generated signals, in transient transfection assays to examine the contribution of the CD28-B7 interaction to IL-2 gene activation. These studies indicate that the CD28-regulated signal transduction pathway is activated during SE stimulation of T cells and plays an important role in SE induction of IL-2 gene expression through its influence upon the CD28-responsive element contained within the IL-2 gene promoter. This effect is particularly profound in the activation of the IL-2 gene in peripheral blood T cells.

scholarly journals Prostaglandin E2 and other cyclic AMP elevating agents inhibit interleukin 2 gene transcription by counteracting calcineurin-dependent pathways.

1993 ◽  
Vol 178 (5) ◽  
pp. 1813-1817 ◽  
Author(s):  
F Paliogianni ◽  
R L Kincaid ◽  
D T Boumpas
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
Prostaglandin E2 ◽  
Gene Transcription ◽  
T Cell Activation ◽  
Promoter Activity ◽  
Cell Activation ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Inhibitory Effects

We have previously shown that prostaglandin E2 and other cAMP elevating agents inhibit the nuclear transcription of the human IL-2 gene by interfering with a Ca(2+)-sensitive T cell signal transduction pathway. Calcineurin, a Ca2+/calmodulin-dependent 2B protein phosphatase, is an essential component of the T cell receptor signal transduction pathway leading to IL-2 gene expression. We have therefore tested the hypothesis that this phosphatase may be a target for the inhibitory effects of cAMP on IL-2 gene transcription. We report here that PGE2 markedly reduces the IL-2 promoter activity that is induced by a constitutively active form of calcineurin. In contrast to the complete inhibition of promoter activity produced by the immunosuppressants cyclosporin A and FK-506, this partial block suggests that PGE2 modulates downstream events needed for lymphokine gene activation. Overexpression of calcineurin in Jurkat cells decreases their apparent sensitivity to the inhibitory effects of PGE2 consistent with the fact that this enzyme plays a physiological role in dephosphorylating substrates of cAMP-dependent kinases in several tissues. These results provide evidence that cAMP-dependent pathways may antagonize calcineurin-regulated cascades for T cell activation in vivo, and suggest crosstalk between the Ca2+ and the cAMP signaling pathways during T cell activation.

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