Glucocorticoid-induced leucine zipper (GILZ) is involved in glucocorticoid-induced and mineralocorticoid-induced leptin production by osteoarthritis synovial fibroblasts.
[en] 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. The purpose of this study was to position GILZ in OA through its involvement in the anti-inflammatory activities of glucocorticoids and/or in the metabolic pathway of leptin induction. The influences of mineralocorticoids on GILZ and leptin expression were also investigated. METHODS: Human synovial fibroblasts were isolated from OA patients during knee replacement surgery. Then, the cells were treated with a glucocorticoid (prednisolone), a mineralocorticoid (aldosterone), a glucocorticoid receptor (GR) antagonist (mifepristone), a selective glucocorticoid receptor agonist (Compound A), mineralocorticoid receptor (MR) antagonists (eplerenone and spironolactone), TNF-alpha or transforming growth factor (TGF)-beta. Cells were transfected with shRNA lentiviruses for the silencing of GILZ and GR. The leptin, IL-6, IL-8 and matrix metalloproteinase (MMP)-1 levels were measured by ELISA. Leptin, the leptin receptor (Ob-R), GR and GILZ expression levels were analyzed by western blotting and/or RT-qPCR. RESULTS: (1) The glucocorticoid prednisolone and the mineralocorticoid aldosterone induced GILZ expression dose-dependently in OA synovial fibroblasts, through GR but not MR. Similar effects on leptin and Ob-R were observed: leptin secretion and Ob-R expression were also induced by prednisolone and aldosterone through GR; (2) GILZ silencing experiments demonstrated that GILZ was involved in the glucocorticoid-induced and mineralocorticoid-induced leptin secretion and Ob-R expression in OA synovial fibroblasts; and (3) GILZ inhibition did not alter the production of pro-inflammatory cytokines by OA synovial fibroblast or the anti-inflammatory properties of glucocorticoids. CONCLUSIONS: The absence of GILZ prevents corticoid-induced leptin and Ob-R expression without affecting the anti-inflammatory properties of glucocorticoids in OA synovial fibroblasts. Mineralocorticoids also induce leptin and Ob-R expression through GILZ.
Deroyer, Céline ; Université de Liège > Département des sciences cliniques > Rhumatologie
Gillet, Philippe ; Université de Liège > Département des sciences cliniques > Chirurgie de l'appareil locomoteur
Louis, Edouard ; Université de Liège > Département des sciences cliniques > Hépato-gastroentérologie
Malaise, Michel ; Université de Liège > Département des sciences cliniques > Rhumatologie
DE SENY, Dominique ; Centre Hospitalier Universitaire de Liège - CHU > Service de rhumatologie
Language :
English
Title :
Glucocorticoid-induced leucine zipper (GILZ) is involved in glucocorticoid-induced and mineralocorticoid-induced leptin production by osteoarthritis synovial fibroblasts.
Yang N, Zhang W, Shi XM. Glucocorticoid-induced leucine zipper (GILZ) mediates glucocorticoid action and inhibits inflammatory cytokine-induced COX-2 expression. J Cell Biochem. 2008;103(6):1760-71.
Yang YH, Aeberli D, Dacumos A, Xue JR, Morand EF. Annexin-1 regulates macrophage IL-6 and TNF via glucocorticoid-induced leucine zipper. J Immunol. 2009;183(2):1435-45.
Eddleston J, Herschbach J, Wagelie-Steffen AL, Christiansen SC, Zuraw BL. The anti-inflammatory effect of glucocorticoids is mediated by glucocorticoid-induced leucine zipper in epithelial cells. J Allergy Clin Immunol. 2007;119(1):115-22.
Esposito E, Bruscoli S, Mazzon E, et al. Glucocorticoid-induced leucine zipper (GILZ) over-expression in T lymphocytes inhibits inflammation and tissue damage in spinal cord injury. Neurotherapeutics. 2012;9(1):210-25.
Luz-Crawford P, Tejedor G, Mausset-Bonnefont AL, et al. Gilz governs the therapeutic potential of mesenchymal stem cells by inducing a switch from pathogenic to regulatory Th17 cells. Arthritis Rheum. 2015;67:1514-24.
Frodl T, Carballedo A, Frey EM, et al. Expression of glucocorticoid inducible genes is associated with reductions in cornu ammonis and dentate gyrus volumes in patients with major depressive disorder. Dev Psychopathol. 2014;26(4 Pt 2):1209-17.
Bruscoli S, Velardi E, Di Sante M, et al. Long glucocorticoid-induced leucine zipper (L-GILZ) protein interacts with ras protein pathway and contributes to spermatogenesis control. J Biol Chem. 2012;287(2):1242-51.
Beaulieu E, Ngo D, Santos L, et al. Glucocorticoid-induced leucine zipper is an endogenous antiinflammatory mediator in arthritis. Arthritis Rheum. 2010;62(9):2651-61.
Ngo D, Beaulieu E, Gu R, et al. Divergent effects of endogenous and exogenous glucocorticoid-induced leucine zipper in animal models of inflammation and arthritis. Arthritis Rheum. 2013;65(5):1203-12.
Cheng Q, Fan H, Ngo D, et al. GILZ overexpression inhibits endothelial cell adhesive function through regulation of NF-kappaB and MAPK activity. J Immunol. 2013;191(1):424-33.
Oliveria SA, Felson DT, Cirillo PA, Reed JI, Walker AM. Body weight, body mass index, and incident symptomatic osteoarthritis of the hand, hip, and knee. Epidemiology. 1999;10(2):161-6.
Yoshimura N, Muraki S, Oka H, et al. Accumulation of metabolic risk factors such as overweight, hypertension, dyslipidaemia, and impaired glucose tolerance raises the risk of occurrence and progression of knee osteoarthritis: a 3-year follow-up of the ROAD study. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society. 2012;20(11):1217-26.
Dumond H, Presle N, Terlain B, et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 2003;48(11):3118-29.
Stannus OP, Cao Y, Antony B, et al. Cross-sectional and longitudinal associations between circulating leptin and knee cartilage thickness in older adults. Ann Rheum Dis. 2015;74(1):82-8.
Griffin TM, Huebner JL, Kraus VB, Guilak F. Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheum. 2009;60(10):2935-44.
Vuolteenaho K, Koskinen A, Moilanen T, Moilanen E. Leptin levels are increased and its negative regulators, SOCS-3 and sOb-R are decreased in obese patients with osteoarthritis: a link between obesity and osteoarthritis. Ann Rheum Dis. 2012;71(11):1912-3.
Yang WH, Liu SC, Tsai CH, et al. Leptin induces IL-6 expression through OBRl receptor signaling pathway in human synovial fibroblasts. PLoS One. 2013;8(9), e75551.
Koskinen A, Vuolteenaho K, Nieminen R, Moilanen T, Moilanen E. Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients. Clin Exp Rheumatol. 2011;29(1):57-64.
Relic B, Zeddou M, Desoroux A, Beguin Y, de Seny D, Malaise MG. Genistein induces adipogenesis but inhibits leptin induction in human synovial fibroblasts. Laboratory investigation; a journal of technical methods and pathology. 2009;89(7):811-22.
Zeddou M, Relic B, Malaise O, et al. Differential signalling through ALK-1 and ALK-5 regulates leptin expression in mesenchymal stem cells. Stem Cells Dev. 2012;21(11):1948-55.
Sundahl N, Bridelance J, Libert C, De Bosscher K, Beck IM. Selective glucocorticoid receptor modulation: new directions with non-steroidal scaffolds. Pharmacol Ther. 2015;152:28-41.
Schacke H, Berger M, Rehwinkel H, Asadullah K. Selective glucocorticoid receptor agonists (SEGRAs): novel ligands with an improved therapeutic index. Mol Cell Endocrinol. 2007;275(1-2):109-17.
Malaise O, Relic B, Quesada-Calvo F, et al. Selective glucocorticoid receptor modulator compound A, in contrast to prednisolone, does not induce leptin or the leptin receptor in human osteoarthritis synovial fibroblasts. Rheumatology. 2014;54:1087-92.
Sun B, Chamarthi B, Williams JS, et al. Different polymorphisms of the mineralocorticoid receptor gene are associated with either glucocorticoid or mineralocorticoid levels in hypertension. J Clin Endocrinol Metab. 2012;97(9):E1825-9.
Ren R, Oakley RH, Cruz-Topete D, Cidlowski JA. Dual role for glucocorticoids in cardiomyocyte hypertrophy and apoptosis. Endocrinology. 2012;153(11):5346-60.
Takahashi K, Murase T, Takatsu M, et al. Roles of oxidative stress and the mineralocorticoid receptor in cardiac pathology in a rat model of metabolic syndrome. Nagoya J Med Sci. 2015;77(1-2):275-89.
Kraus D, Jager J, Meier B, Fasshauer M, Klein J. Aldosterone inhibits uncoupling protein-1, induces insulin resistance, and stimulates proinflammatory adipokines in adipocytes. Horm Metab Res. 2005;37(7):455-9.
Ueda K, Fujiki K, Shirahige K, et al. Genome-wide analysis of murine renal distal convoluted tubular cells for the target genes of mineralocorticoid receptor. Biochem Biophys Res Commun. 2014;445(1):132-7.
Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006;(2):CD005328.
Celeste C, Ionescu M, Robin Poole A, Laverty S. Repeated intraarticular injections of triamcinolone acetonide alter cartilage matrix metabolism measured by biomarkers in synovial fluid. J Orthop Res. 2005;23(3):602-10.
Fubini SL, Todhunter RJ, Burton-Wurster N, Vernier-Singer M, MacLeod JN. Corticosteroids alter the differentiated phenotype of articular chondrocytes. J Orthop Res. 2001;19(4):688-95.
Riccardi C, Bruscoli S, Ayroldi E, Agostini M, Migliorati G. GILZ, a glucocorticoid hormone induced gene, modulates T lymphocytes activation and death through interaction with NF-kB. Adv Exp Med Biol. 2001;495:31-9.
Ayroldi E, Migliorati G, Bruscoli S, et al. Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB. Blood. 2001;98(3):743-53.
Berrebi D, Bruscoli S, Cohen N, et al. Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10. Blood. 2003;101(2):729-38.
Keenan CR, Mok JS, Harris T, Xia Y, Salem S, Stewart AG. Bronchial epithelial cells are rendered insensitive to glucocorticoid transactivation by transforming growth factor-beta1. Respir Res. 2014;15:55.
Drebert Z, Bracke M, Beck IM. Glucocorticoids and the non-steroidal selective glucocorticoid receptor modulator, compound A, differentially affect colon cancer-derived myofibroblasts. J Steroid Biochem Mol Biol. 2015;149:92-105.
Gavrila A, Chachi L, Tliba O, Brightling C, Amrani Y. Effect of the plant derivative Compound A on the production of corticosteroid-resistant chemokines in airway smooth muscle cells. Am J Respir Cell Mol Biol. 2015;53(5):728-37.
Reber LL, Daubeuf F, Plantinga M, et al. A dissociated glucocorticoid receptor modulator reduces airway hyperresponsiveness and inflammation in a mouse model of asthma. J Immunol. 2012;188(7):3478-87.
Liu J, Zhang M, Niu C, et al. Dexamethasone inhibits repair of human airway epithelial cells mediated by glucocorticoid-induced leucine zipper (GILZ). PLoS One. 2013;8(4), e60705.
Bruscoli S, Donato V, Velardi E, et al. Glucocorticoid-induced leucine zipper (GILZ) and long GILZ inhibit myogenic differentiation and mediate anti-myogenic effects of glucocorticoids. J Biol Chem. 2010;285(14):10385-96.
Iacobellis G, Petramala L, Cotesta D, et al. Adipokines and cardiometabolic profile in primary hyperaldosteronism. J Clin Endocrinol Metab. 2010;95(5):2391-8.
Musani SK, Vasan RS, Bidulescu A, et al. Aldosterone, C-reactive protein, and plasma B-type natriuretic peptide are associated with the development of metabolic syndrome and longitudinal changes in metabolic syndrome components: findings from the Jackson Heart Study. Diabetes Care. 2013;36(10):3084-92.
Cooper JN, Fried L, Tepper P, et al. Changes in serum aldosterone are associated with changes in obesity-related factors in normotensive overweight and obese young adults. Hypertens Res. 2013;36(10):895-901.
Sherajee SJ, Rafiq K, Nakano D, et al. Aldosterone aggravates glucose intolerance induced by high fructose. Eur J Pharmacol. 2013;720(1-3):63-8.
Rovensky J, Kvetnansky R, Radikova Z, et al. Hormone concentrations in synovial fluid of patients with rheumatoid arthritis. Clin Exp Rheumatol. 2005;23(3):292-6.
Lee MJ, Fried SK. The glucocorticoid receptor, not the mineralocorticoid receptor, plays the dominant role in adipogenesis and adipokine production in human adipocytes. Int J Obes (Lond). 2014;38(9):1228-33.
Leminen R, Raivio T, Ranta S, et al. Late follicular phase administration of mifepristone suppresses circulating leptin and FSH - mechanism(s) of action in emergency contraception? Eur J Endocrinol. 2005;152(3):411-8.
Guo C, Ricchiuti V, Lian BQ, et al. Mineralocorticoid receptor blockade reverses obesity-related changes in expression of adiponectin, peroxisome proliferator-activated receptor-gamma, and proinflammatory adipokines. Circulation. 2008;117(17):2253-61.
