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Charlotte L George, Matthew T Birnie, Benjamin Flynn, Yvonne Kershaw, Stafford L Lightman, Becky L Conway-Campbell
In this paper we report differential decoding of the ultradian corticosterone signal by glucocorticoid target tissues. Pulsatile corticosterone replacement in adrenalectomised rats resulted in different dynamics of Sgk1 mRNA production, with a distinct pulsatile mRNA induction profile observed in the pituitary in contrast to a non-pulsatile induction in the prefrontal cortex. We further report the first evidence for pulsatile transcriptional repression of a glucocorticoid-target gene in vivo, with pulsatile regulation of Pomc transcription in pituitary...
October 18, 2016: Molecular and Cellular Endocrinology
Mythily Srinivasan, Baindu Bayon, Nipun Chopra, Debomoy K Lahiri
In the central nervous system (CNS), activation of the transcription factor nuclear factor-kappa B (NF-κβ) is associated with both neuronal survival and increased vulnerability to apoptosis. The mechanisms underlying these dichotomous effects are attributed to the composition of NF-κΒ dimers. In Alzheimer's disease (AD), β-amyloid (Aβ) and other aggregates upregulate activation of p65:p50 dimers in CNS cells and enhance transactivation of pathological mediators that cause neuroinflammation and neurodegeneration...
2016: PloS One
InKyeom Kim
Histone deacetylases (HDACs) act as co-repressors in gene transcription by erasing the acetylation of histones, resulting in epigenetic gene silencing. Recent studies revealed that HDAC inhibitors attenuated blood pressure of several hypertensive animal models such as spontaneously hypertensive rats, hyperaldosteronism rats, angiotensin II-induced hypertensive rats and pulmonary hypertensive rats. Unexpectedly, microarray studies uncovered that administration of HDAC inhibitors decreased expression of some genes for example extracellular matrix proteins, oxidative stress-related proteins, cytokines, chemokines and ion transporters, mostly targets of corticoid receptors...
September 2016: Journal of Hypertension
Olivier Malaise, Biserka Relic, Edith Charlier, Mustapha Zeddou, Sophie Neuville, Céline Deroyer, Philippe Gillet, Edouard Louis, Michel G Malaise, Dominique de Seny
BACKGROUND: Glucocorticoid-induced leucine zipper (GILZ) is a mediator of the anti-inflammatory activities of glucocorticoids. However, GILZ deletion does not impair the anti-inflammatory activities of exogenous glucocorticoids in mice arthritis models and GILZ could also mediate some glucocorticoid-related adverse events. Osteoarthritis (OA) is a metabolic disorder that is partly attributed to adipokines such as leptin, and we previously observed that glucocorticoids induced leptin secretion in OA synovial fibroblasts...
October 4, 2016: Arthritis Research & Therapy
InKyeom Kim
Histone deacetylases (HDACs) act as co-repressors in gene transcription by erasing the acetylation of histones, resulting in epigenetic gene silencing. Recent studies revealed that HDAC inhibitors attenuated blood pressure of several hypertensive animal models such as spontaneously hypertensive rats, hyperaldosteronism rats, angiotensin II-induced hypertensive rats and pulmonary hypertensive rats. Unexpectedly, microarray studies uncovered that administration of HDAC inhibitors decreased expression of some genes for example extracellular matrix proteins, oxidative stress-related proteins, cytokines, chemokines and ion transporters, mostly targets of corticoid receptors...
September 2016: Journal of Hypertension
Jessica Hoppstädter, Nina Hachenthal, Jenny Vanessa Valbuena-Perez, Sebastian Lampe, Ksenia Astanina, Michael M Kunze, Stefano Bruscoli, Carlo Riccardi, Tobias Schmid, Britta Diesel, Alexandra K Kiemer
GILZ is inducible by glucocorticoids and plays a key role in their mode of action. GILZ attenuates inflammation mainly by inhibition of NF-κB and MAP kinase activation but does not seem to be involved in the severe side effects observed after glucocorticoid treatment. Therefore, GILZ might be a promising target for new therapeutic approaches. The present work focuses on the natural product curcumin, which has previously been reported to inhibit NF-κB. GILZ was inducible by curcumin in macrophage cell lines, primary human monocyte-derived macrophages, and murine bone marrow-derived macrophages (BMMs)...
September 14, 2016: Journal of Biological Chemistry
L Chachi, M Abbasian, A Gavrila, A Alzahrani, O Tliba, P Bradding, A J Wardlaw, C Brightling, Y Amrani
BACKGROUND: The mechanisms driving glucocorticoid (GC) insensitivity in patients with severe asthma are still unknown. Recent evidence suggests the existence of GC-insensitive pathways in airway smooth muscle (ASM) caused by a defect in GC receptor (GRα) function. We examined whether other mechanisms could potentially explain the reduced sensitivity of ASM cells to GC in severe asthmatics. METHODS: Airway smooth muscle cells from healthy and severe asthmatic subjects were treated with TNF-α and responses to corticosteroids in both cohorts were compared by ELISA, immunoblot, immunohistochemistry and real-time PCR...
August 9, 2016: Allergy
Yasmine Touil, Pascaline Segard, Pauline Ostyn, Severine Begard, Caroline Aspord, Raja El Machhour, Bernadette Masselot, Jerome Vandomme, Pilar Flamenco, Thierry Idziorek, Martin Figeac, Pierre Formstecher, Bruno Quesnel, Renata Polakowska
Metastatic cancer relapses following the reactivation of dormant, disseminated tumour cells; however, the cells and factors involved in this reactivation are just beginning to be identified. Using an immunotherapy-based syngeneic model of melanoma dormancy and GFP-labelled dormant cell-derived cell lines, we determined that vaccination against melanoma prevented tumour growth but did not prevent tumour cell dissemination or eliminate all tumour cells. The persistent disseminated melanoma tumour cells were quiescent and asymptomatic for one year...
2016: Scientific Reports
Fanny André, Paola Corazao-Rozas, Thierry Idziorek, Bruno Quesnel, Jérome Kluza, Philippe Marchetti
The Glucocorticoïd-induced leucine zipper (GILZ) protein has profound anti-inflammatory activities in haematopoietic cells. GILZ regulates numerous signal transduction pathways involved in proliferation and survival of normal and neoplastic cells. Here, we have demonstrated the potential of GILZ in alleviating apoptosis induced by ER stress inducers. Whereas the glucocorticoid, dexamethasone, protects from tunicamycin-induced cell death, silencing endogeneous GILZ in dexamethasone-treated cancer cells alter the capacity of glucocorticoids to protect from tunicamycin-mediated apoptosis...
September 16, 2016: Biochemical and Biophysical Research Communications
Eva Kassi, Narjes Nasiri-Ansari, Eliana Spilioti, Vassiliki Kalotychou, Panagiota E Apostolou, Paraskevi Moutsatsou, Athanasios G Papavassiliou
Glucocorticoids (GCs) are widely used in the treatment of inflammatory and autoimmune diseases; however, patients are often resistant to GC effects. Current studies indicate that vitamin D reduces the risk or modifies the course of autoimmune diseases posing vitamin D supplementation as a prevention or therapeutic option. Herein, we investigated whether vitamin D can modify the response to GCs at the molecular level. To this end, peripheral blood mononuclear cells (PBMCs) were isolated from healthy vitamin D-deficient women and incubated with either the active metabolite 1,25(OH)2D3 (VitD) for 11 days or dexamethasone (Dex) for the last 2 days in the presence or absence of VitD...
May 24, 2016: Cellular and Molecular Life Sciences: CMLS
Mi-Jeong Lee, Rong-Ze Yang, Kalypso Karastergiou, Steven R Smith, Jeffery R Chang, Da-Wei Gong, Susan K Fried
The glucocorticoid-induced leucine zipper (GILZ), a primary target of glucocorticoids, is expressed in human adipocytes, but its importance in adipocyte function is unknown. Because TNFα is increased in obese adipose tissue and antagonizes a number of glucocorticoid actions, we investigated the interplay of these pathways. GILZ knockdown increased and GILZ overexpression decreased interleukin-6 (IL-6) and leptin mRNA and protein secretion. GILZ knockdown increased the magnitude of the glucocorticoid effect on leptin secretion, but did not affect the glucocorticoid suppression of IL-6...
July 2016: Journal of Lipid Research
M Soták, J Bryndová, P Ergang, K Vagnerová, P Kvapilová, M Vodička, J Pácha, A Sumová
Glucocorticoids are considered to synchronize the rhythmicity of clock genes in peripheral tissues; however, the role of circadian variations of endogenous glucocorticoids is not well defined. In the present study, we examined whether peripheral circadian clocks were impaired by adrenalectomy. To achieve this, we tested the circadian rhythmicity of core clock genes (Bmal1, Per1-3, Cry1, RevErbα, Rora), clock-output genes (Dbp, E4bp4) and a glucocorticoid- and clock-controlled gene (Gilz) in liver, jejunum, kidney cortex, splenocytes and visceral adipose tissue (VAT)...
2016: Chronobiology International
Olivier Robert, Hédia Boujedidi, Amélie Bigorgne, Gladys Ferrere, Cosmin Sebastian Voican, Sabine Vettorazzi, Jan Peter Tuckermann, Laurence Bouchet-Delbos, Thi Tran, Patrice Hemon, Virginie Puchois, Ibrahim Dagher, Richard Douard, Francoise Gaudin, Hélène Gary-Gouy, Francis Capel, Ingrid Durand-Gasselin, Sophie Prévot, Sophie Rousset, Sylvie Naveau, Véronique Godot, Dominique Emilie, Marc Lombès, Gabriel Perlemuter, Anne-Marie Cassard
BACKGROUND & AIMS: Kupffer cells (KC) play a key role in the onset of inflammation in non-alcoholic steatohepatitis (NASH). The glucocorticoid receptor (GR) induces glucocorticoid-induced leucine zipper (GILZ) expression in monocytes/macrophages and is involved in several inflammatory processes. We hypothesized that the GR-GILZ axis in KC may contribute to the pathophysiology of obesity-induced liver inflammation. METHODS: By using a combination of primary cell culture, pharmacological experiments, mice deficient for the Gr specifically in macrophages and transgenic mice overexpressing Gilz in macrophages, we explored the involvement of the Gr-Gilz axis in KC in the pathophysiology of obesity-induced liver inflammation...
April 2016: Journal of Hepatology
Simona Ronchetti, Graziella Migliorati, Carlo Riccardi
Glucocorticoid-induced leucine zipper (GILZ) is a dexamethasone-inducible gene that mediates glucocorticoid (GC) actions in a variety of cell types, including many cells of immune system. In particular, GILZ can control T cell activities, such as activation and differentiation, mainly through its ability to homo- and hetero-dimerize with partner proteins, such as NF-κB, Ras, and C/EBP. These protein-protein interactions control the regulation of pro-inflammatory target genes. A number of in vitro and in vivo studies using mouse models of inflammatory diseases demonstrate an anti-inflammatory role for GILZ...
2015: Frontiers in Endocrinology
Sarah A Jones, Andrew E J Toh, Dragana Odobasic, Marie-Anne Virginie Oudin, Qiang Cheng, Jacinta P W Lee, Stefan J White, Brendan E Russ, Simona Infantino, Amanda Light, David M Tarlinton, James Harris, Eric F Morand
OBJECTIVES: Systemic lupus erythematosus (SLE) is a serious multisystem autoimmune disease, mediated by disrupted B cell quiescence and typically treated with glucocorticoids. We studied whether B cells in SLE are regulated by the glucocorticoid-induced leucine zipper (GILZ) protein, an endogenous mediator of anti-inflammatory effects of glucocorticoids. METHODS: We conducted a study of GILZ expression in blood mononuclear cells of patients with SLE, performed in vitro analyses of GILZ function in mouse and human B cells, assessed the contributions of GILZ to autoimmunity in mice, and used the nitrophenol coupled to keyhole limpet haemocyanin model of immunisation in mice...
April 2016: Annals of the Rheumatic Diseases
Cynthia de Souza Ferreira, Lucilia de Fátima dd Sousa Fomes, Gilze Espirito Santo da Silva, Glorimar Rosa
INTRODUCTION: chia is a seed rich in such nutrients as proteins, n-3 fatty acids and especially alpha-linolenic acid (ALA), minerals, fibers and antioxidants. Efforts have been made to assess whether human consumption of chia can reduce cardiovascular risk factors; however, it has not been established as effective and the findings of the few studies to have looked into the matter are inconsistent. AIM: to systematize the findings of studies assessing the effect the consumption of chia seed, either milled or whole, has in the prevention/control of cardiovascular risk factors in humans...
2015: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
Adedoyin Igunnu, Young-Mi Seok, Lawrence A Olatunji, Seol-Hee Kang, Inkyeom Kim
Clinical studies have shown that the use of combined oral contraceptive in pre-menopausal women is associated with fluid retention. However, the molecular mechanism is still elusive. We hypothesized that combined oral contraceptive (COC) ethinyl estradiol (EE) and norgestrel (N) synergistically activates mineralocorticoid receptor (MR) through histone code modifications. Twelve-week-old female Sprague-Dawley rats were treated with olive oil (control), a combination of 0.1µg EE and 1.0µg N (low COC) or 1.0µg EE and 10...
December 15, 2015: European Journal of Pharmacology
Marie-Alix Espinasse, Aurélie Pépin, Pauline Virault-Rocroy, Natacha Szely, Sylvie Chollet-Martin, Marc Pallardy, Armelle Biola-Vidamment
Glucocorticoid-induced leucine zipper (GILZ) is a potent anti-inflammatory protein, the expression of which is mainly induced by glucocorticoids (GCs) in haematopoietic cells. GILZ regulates signal transduction pathways of inflammation and plays a role in cell survival. The objective of this study was to evaluate the expression and mechanisms of action of GILZ in the apoptosis of human neutrophils. GILZ expression was induced by GCs in human neutrophils, enhanced upon phosphatidylinositol 3-kinase inhibition and resulted in apoptosis amplification...
2016: Journal of Innate Immunity
Charlotte Kervoëlen, Emmanuelle Ménoret, Patricia Gomez-Bougie, Régis Bataille, Catherine Godon, Séverine Marionneau-Lambot, Philippe Moreau, Catherine Pellat-Deceunynck, Martine Amiot
Due to its cytotoxic effect in lymphoid cells, dexamethasone is widely used in the treatment of multiple myeloma (MM). However, only a subset of myeloma patients responds to high-dose dexamethasone. Despite the undeniable anti-myeloma benefits of dexamethasone, significant adverse effects have been reported. We re-evaluate the anti-tumor effect of dexamethasone according to the molecular heterogeneity of MM. We demonstrated that the pro-death effect of dexamethasone is related to the genetic heterogeneity of MM because sensitive cell lines were restricted to MAF and MMSET signature subgroups, whereas all CCND1 cell lines (n = 10) were resistant to dexamethasone...
September 29, 2015: Oncotarget
Truls Gråberg, Lovisa Strömmer, Erik Hedman, Mehmet Uzunel, Ewa Ehrenborg, Ann-Charlotte Wikström
INTRODUCTION: An 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 METHODS: Changes 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)...
2015: Journal of Inflammation Research
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