TY - JOUR
T1 - The role and effects of glucocorticoid-induced leucine zipper in the context of inflammation resolution
AU - Vago da Silva, Juliana Priscila
AU - Tavares, Luciana Padua
AU - Garcia, Cristiana Couto
AU - Lima, Katia Maciel
AU - Perucci, Luiza Oliveira
AU - Vieira, Erica Leandro Marciano
AU - Nogueira, Camila R C
AU - Soriani, Frederico Marianetti
AU - Martins, Joilson de Oliveira
AU - Silva, Patricia Machado Rodrigues
AU - Gomes, Karina Braga
AU - Pinho, Vanessa
AU - Bruscoli, Stefano
AU - Riccardi, Carlo
AU - Beaulieu, Elaine Vicky
AU - Morand, Eric Francis
AU - Teixeira, Mauro Martin
AU - Sousa, Lirlandia Pires de
PY - 2015
Y1 - 2015
N2 - 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-kappaB 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.
AB - 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-kappaB 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.
UR - http://www.jimmunol.org/content/194/10/4940.full.pdf+html
U2 - 10.4049/jimmunol.1401722
DO - 10.4049/jimmunol.1401722
M3 - Article
SN - 0022-1767
VL - 194
SP - 4940
EP - 4950
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -