title: The role and effects of glucocorticoid-induced leucine zipper in the context of inflammation resolution.
abstract: Glucocorticoid (GC)-induced leucine zipper (GILZ) has been shown to mediate or mimic several actions of GC. This study assessed the role of GILZ in self-resolving and GC-induced resolution of neutrophilic inflammation induced by LPS in mice. GILZ expression was increased during the resolution phase of LPS-induced pleurisy, especially in macrophages with resolving phenotypes. Pretreating LPS-injected mice with trans-activator of transcription peptide (TAT)-GILZ, a cell-permeable GILZ fusion protein, shortened resolution intervals and improved resolution indices. Therapeutic administration of TAT-GILZ induced inflammation resolution, decreased cytokine levels, and promoted caspase-dependent neutrophil apoptosis. TAT-GILZ also modulated the activation of the survival-controlling proteins ERK1/2, NF-κB and Mcl-1. GILZ deficiency was associated with an early increase of annexin A1 (AnxA1) and did not modify the course of neutrophil influx induced by LPS. Dexamethasone treatment resolved inflammation and induced GILZ expression that was dependent on AnxA1. Dexamethasone-induced resolution was not altered in GILZ(-/-) mice due to compensatory expression and action of AnxA1. Our results show that therapeutic administration of GILZ efficiently induces a proapoptotic program that promotes resolution of neutrophilic inflammation induced by LPS. Alternatively, a lack of endogenous GILZ during the resolution of inflammation is compensated by AnxA1 overexpression.
authors: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil;
authors: Juliana P
authors: JP
authors: Vago
authors: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil;
authors: Luciana P
authors: LP
authors: Tavares
authors: Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Laboratório de Vírus Respiratórios e do Sarampo, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro 21040-360, Brazil;
authors: Cristiana C
authors: CC
authors: Garcia
authors: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil;
authors: Kátia M
authors: KM
authors: Lima
authors: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil;
authors: Luiza O
authors: LO
authors: Perucci
authors: Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil;
authors: Érica L
authors: ÉL
authors: Vieira
authors: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil;
authors: Camila R C
authors: CR
authors: Nogueira
authors: Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil;
authors: Frederico M
authors: FM
authors: Soriani
authors: Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo 05508-900, Brazil;
authors: Joilson O
authors: JO
authors: Martins
authors: Laboratório de Inflamação, Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro 21040-360, Brazil;
authors: Patrícia M R
authors: PM
authors: Silva
authors: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil;
authors: Karina B
authors: KB
authors: Gomes
authors: Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil;
authors: Vanessa
authors: V
authors: Pinho
authors: Section of Pharmacology, Department of Medicine, University of Perugia, 06132 Perugia, Italy; and.
authors: Stefano
authors: S
authors: Bruscoli
authors: Section of Pharmacology, Department of Medicine, University of Perugia, 06132 Perugia, Italy; and.
authors: Carlo
authors: C
authors: Riccardi
authors: Monash University Centre for Inflammatory Diseases, Monash Medical Centre, Clayton, Victoria 3168, Australia.
authors: Elaine
authors: E
authors: Beaulieu
authors: Monash University Centre for Inflammatory Diseases, Monash Medical Centre, Clayton, Victoria 3168, Australia.
authors: Eric F
authors: EF
authors: Morand
authors: Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; lipsousa72@gmail.com mmtex@icb.ufmg.br.
authors: Mauro M
authors: MM
authors: Teixeira
authors: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil; lipsousa72@gmail.com mmtex@icb.ufmg.br.
authors: Lirlândia P
authors: LP
authors: Sousa
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D002465:Cell Movement; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010998:Pleurisy / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000276:immunology*
chemical_list: D017305:Annexin A1; C498608:Dsip1 protein, mouse; D008070:Lipopolysaccharides; D014157:Transcription Factors