1,720,992 research outputs found
Glucocorticoid-Induced Leucine Zipper: A Novel Anti-inflammatory Molecule
Full text linkGlucocorticoids (GCs) are the most commonly used drugs for treatment of autoimmune and inflammatory diseases. Their efficacy is due to their ability to bind cytoplasmic receptors (glucocorticoid receptors, GR) and other cytoplasmic proteins, thus regulating gene expression. Although GCs are potent life-saving drugs, their therapeutic effects are transitory and chronic use of GCs is accompanied by serious side effects. Therefore, new drugs are needed to replace GCs. We have identified a gene, glucocorticoid-induced leucine zipper (GILZ or tsc22d3), that is rapidly and invariably induced by GCs. Human GILZ is a 135-amino acid protein that mediates many GC effects, including inhibition of the NF-κB and MAPK pathways. Similar to GCs, GILZ exerts anti-inflammatory activity in experimental disease models, including inflammatory bowel diseases and arthritis. While transgenic mice that overexpress GILZ are more resistant, GILZ knockout mice develop worse inflammatory diseases. Moreover, the anti-inflammatory effect of GCs is attenuated in GILZ-deficient mice. Importantly, in vivo delivery of recombinant GILZ protein cured colitis and facilitated resolution of lipopolysaccharide-induced inflammation without apparent toxic effects. A synthetic GILZ-derived peptide, corresponding to the GILZ region that interacts with NF-κB, was able to suppress experimental autoimmune encephalomyelitis. Collectively, these findings indicate that GILZ is an anti-inflammatory molecule that may serve as the basis for designing new therapeutic approaches to inflammatory diseases
Anti-inflammatory activity and neuroprotective effects of glucocorticoid-induced leucine zipper (GILZ)
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Anti-inflammatory activity and neuroprotective effects of glucocorticoid-induced leucine zipper (GILZ)
No full textGlucocorticoid Induced Leucine Zipper (GILZ) is required for hematopoietic stem cell function
No full textREGULATION OF HEMATOPOIETIC STEM CELL (HSC) DEVELOPMENT: ROLE OF GLUCOCORTICOID INDUCED LEUCINE ZIPPER (GILZ)
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
GLUCOCORTICOID-INDUCED LEUCINE ZIPPER (GILZ) INTRINSICALLY REGULATES HEMATOPOIETIC STEM CELL FUNCTION
No full textThe maintenance of hematopoietic stem cells (HSC) is linked to their quiescent state, while HSC proliferation is associated with differentiation and a loss of long-term stem cell potential. The balance between HSC quiescence and proliferation is tightly regulated by intrinsic and extrinsic cues in the bone marrow. Endogenous glucocorticoid hormones (GC) regulate HSC homing via control of CXCR4 expression. Glucocorticoid- Induced Leucine Zipper (GILZ) is a gene rapidly induced by GC. It mediates many of GC’ anti-proliferative and anti-inflammatory effects in several cell types. We found that GILZ is expressed in HSC and addressed its role in hematopoiesis using GILZ knock-out (KO) mice. At steady state, young GILZ-KO mice did not show alteration in HSC number and lineage commitment compared to WT mice. However, com- petitive transplantation studies revealed a significant decrease in the fre- quency and number of GILZ-KO compared to WT HSC, suggesting that GILZ-deficient HSC have competitive disadvantage compared to WT cells. RNAseq analysis of gene expression revealed several deregulated cellular pathways implicated in HSC function in GILZ KO compared to WT HSC. Importantly, Gene Set Enrichment Analysis showed a signifi- cant depletion of the HSC signature and an enrichment in the mTOR signalling signature in GILZ deficient HSC. Consistently, GILZ deficient HSC showed enhanced proliferation as revealed by flow cytomery analy- sis of Ki67 expression and DNA content. Mice transplanted with GILZ deficient cells showed significantly earlier mortality compared to WT cells-transplanted mice in 5-FU treatment experiments, demonstrating a cell-intrinsic role of GILZ in HSC function. Overall, these data identify GILZ is a novel regulator of HSCs function
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