GILZ as a Mediator of the Anti-Inflammatory Effects of Glucocorticoids

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. Here, authors summarize the studies that make GILZ eligible as an anti-inflammatory protein through which GCs can act. These findings permit the future development of pharmacological tools that mimic the therapeutic effects of GCs while avoiding the detrimental ones.

[1]  E. Mazzon,et al.  Lack of glucocorticoid-induced leucine zipper (GILZ) deregulates B-cell survival and results in B-cell lymphocytosis in mice. , 2015, Blood.

[2]  E. Morand,et al.  GILZ regulates Th17 responses and restrains IL-17-mediated skin inflammation. , 2015, Journal of autoimmunity.

[3]  C. Riccardi,et al.  Glucocorticoid-Induced Leucine Zipper: A Critical Factor in Macrophage Endotoxin Tolerance , 2015, The Journal of Immunology.

[4]  C. Riccardi,et al.  The Role and Effects of Glucocorticoid-Induced Leucine Zipper in the Context of Inflammation Resolution , 2015, The Journal of Immunology.

[5]  C. Riccardi,et al.  Targeting glucocorticoid side effects: selective glucocorticoid receptor modulator or glucocorticoid‐induced leucine zipper? A perspective , 2014, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[6]  Y. Tabata,et al.  Hepatocyte Growth Factor Limits Autoimmune Neuroinflammation via Glucocorticoid-Induced Leucine Zipper Expression in Dendritic Cells , 2014, The Journal of Immunology.

[7]  E. Morand,et al.  Development of novel treatment strategies for inflammatory diseases—similarities and divergence between glucocorticoids and GILZ , 2014, Front. Pharmacol..

[8]  H. Huwer,et al.  Downregulation of the glucocorticoid-induced leucine zipper (GILZ) promotes vascular inflammation. , 2014, Atherosclerosis.

[9]  Nianlan Yang,et al.  Role of Glucocorticoid-induced Leucine Zipper (GILZ) in Bone Acquisition* , 2014, The Journal of Biological Chemistry.

[10]  M. Humbert,et al.  Enhanced glucocorticoid‐induced leucine zipper in dendritic cells induces allergen‐specific regulatory CD4+T‐cells in respiratory allergies , 2014, Allergy.

[11]  C. Riccardi,et al.  GILZ promotes production of peripherally induced Treg cells and mediates the crosstalk between glucocorticoids and TGF-β signaling. , 2014, Cell reports.

[12]  C. Strehl,et al.  Optimized glucocorticoid therapy: Teaching old drugs new tricks , 2013, Molecular and Cellular Endocrinology.

[13]  M. Hickey,et al.  GILZ Overexpression Inhibits Endothelial Cell Adhesive Function through Regulation of NF-κB and MAPK Activity , 2013, The Journal of Immunology.

[14]  C. Libert,et al.  LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome , 2013, EMBO molecular medicine.

[15]  P. O'Byrne,et al.  Corticosteroid‐induced gene expression in allergen‐challenged asthmatic subjects taking inhaled budesonide , 2012, British journal of pharmacology.

[16]  B. Quesnel,et al.  GILZ inhibits the mTORC2/AKT pathway in BCR-ABL+ cells , 2011, Oncogene.

[17]  M. Srinivasan,et al.  Novel p65 Binding Glucocorticoid-induced Leucine Zipper Peptide Suppresses Experimental Autoimmune Encephalomyelitis , 2011, The Journal of Biological Chemistry.

[18]  E. Mazzon,et al.  Glucocorticoid-Induced Leucine Zipper (GILZ) Over-Expression in T Lymphocytes Inhibits Inflammation and Tissue Damage in Spinal Cord Injury , 2011, Neurotherapeutics.

[19]  Daniël P. Melters,et al.  Glucocorticoid-induced Leucine Zipper 1 Stimulates the Epithelial Sodium Channel by Regulating Serum- and Glucocorticoid-induced Kinase 1 Stability and Subcellular Localization* , 2010, The Journal of Biological Chemistry.

[20]  D. Scherman,et al.  Glucocorticoid-induced leucine zipper is an endogenous antiinflammatory mediator in arthritis. , 2010, Arthritis and rheumatism.

[21]  J. Bertoglio,et al.  Glucocorticoid-induced Leucine Zipper (GILZ) Promotes the Nuclear Exclusion of FOXO3 in a Crm1-dependent Manner , 2009, The Journal of Biological Chemistry.

[22]  C. Riccardi,et al.  Glucocorticoid‐induced leucine zipper (GILZ): a new important mediator of glucocorticoid action , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[23]  E. Mazzon,et al.  Glucocorticoid-induced leucine zipper is protective in Th1-mediated models of colitis. , 2009, Gastroenterology.

[24]  Nianlan Yang,et al.  Glucocorticoid‐induced leucine zipper (GILZ) mediates glucocorticoid action and inhibits inflammatory cytokine‐induced COX‐2 expression , 2008, Journal of cellular biochemistry.

[25]  Nianlan Yang,et al.  Regulation of Mesenchymal Stem Cell Osteogenic Differentiation by Glucocorticoid-induced Leucine Zipper (GILZ)* , 2008, Journal of Biological Chemistry.

[26]  C. Riccardi,et al.  GILZ mediates the antiproliferative activity of glucocorticoids by negative regulation of Ras signaling. , 2007, The Journal of clinical investigation.

[27]  C. Gleissner,et al.  IL‐10 inhibits endothelium‐dependent T cell costimulation by up‐regulation of ILT3/4 in human vascular endothelial cells , 2007, European journal of immunology.

[28]  P. J. Sjöström,et al.  Glucocorticoid-induced leucine zipper (GILZ)/NF-κB interaction: role of GILZ homo-dimerization and C-terminal domain , 2005, Nucleic acids research.

[29]  M. Wendl This is an Open Access article distribut... , 2007 .

[30]  C. Riccardi,et al.  Inhibited cell death, NF-kappaB activity and increased IL-10 in TCR-triggered thymocytes of transgenic mice overexpressing the glucocorticoid-induced protein GILZ. , 2006, International immunopharmacology.

[31]  E. Mazzon,et al.  Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines. , 2006, Blood.

[32]  Jian Wang,et al.  A Novel Role for Glucocorticoid-induced Leucine Zipper Protein in Epithelial Sodium Channel-mediated Sodium Transport* , 2005, Journal of Biological Chemistry.

[33]  M. Lombès,et al.  FoxO3 mediates antagonistic effects of glucocorticoids and interleukin-2 on glucocorticoid-induced leucine zipper expression. , 2005, Molecular endocrinology.

[34]  C. Riccardi,et al.  Decrease of Bcl-xL and augmentation of thymocyte apoptosis in GILZ overexpressing transgenic mice. , 2004, Blood.

[35]  C. Akdis,et al.  Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma. , 2004, The Journal of allergy and clinical immunology.

[36]  D. Firsov,et al.  Mineralocorticoid effects in the kidney: correlation between alphaENaC, GILZ, and Sgk-1 mRNA expression and urinary excretion of Na+ and K+. , 2003, Journal of the American Society of Nephrology : JASN.

[37]  B. Song,et al.  A glucocorticoid‐induced leucine‐zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells , 2003, EMBO reports.

[38]  W. Almawi,et al.  Negative regulation of nuclear factor-kappaB activation and function by glucocorticoids. , 2002, Journal of molecular endocrinology.

[39]  D. Reid,et al.  Activation of the inducible nitric oxide synthase pathway contributes to inflammation-induced osteoporosis by suppressing bone formation and causing osteoblast apoptosis. , 2001, Arthritis and rheumatism.

[40]  J. Ashwell,et al.  Inhibition of AP-1 by the Glucocorticoid-inducible Protein GILZ* , 2001, The Journal of Biological Chemistry.

[41]  C. Riccardi,et al.  Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB. , 2001, Blood.

[42]  C. Riccardi,et al.  GILZ, a glucocorticoid hormone induced gene, modulates T lymphocytes activation and death through interaction with NF-kB. , 2001, Advances in experimental medicine and biology.

[43]  C. Riccardi,et al.  A new dexamethasone-induced gene of the leucine zipper family protects T lymphocytes from TCR/CD3-activated cell death. , 1997, Immunity.