title: Role of the glucocorticoid-induced leucine zipper gene in dexamethasone-induced inhibition of mouse neutrophil migrationviacontrol of annexin A1 expression.
abstract: The glucocorticoid-induced leucine zipper (GILZ) gene is a pivotal mediator of the anti-inflammatory effects of glucocorticoids (GCs) that are known to regulate the function of both adaptive and innate immunity cells. Our aim was to investigate the role of GILZ in GC-induced inhibition of neutrophil migration, as this role has not been investigated before. We found that GILZ expression was induced by dexamethasone (DEX), a synthetic GC, in neutrophils, and that it regulated migration of these cells into inflamed tissues under DEX treatment. Of note, inhibition of neutrophil migration was not observed inGILZ-knockout mice with peritonitis that were treated by DEX. This was because DEX was unable to up-regulate annexin A1 (Anxa1) expression in the absence of GILZ. Furthermore, we showed that GILZ mediates Anxa1 induction by GCs by transactivating Anxa1 expression at the promoter levelviabinding with the transcription factor, PU.1. The present findings shed light on the role of GILZ in the mechanism of induction of Anxa1 by GCs. As Anxa1 is an important protein for the resolution of inflammatory response, GILZ may represent a new pharmacologic target for treatment of inflammatory diseases.-Ricci, E., Ronchetti, S., Pericolini, E., Gabrielli, E., Cari, L., Gentili, M., Roselletti, E., Migliorati, G., Vecchiarelli, A., Riccardi, C. Role of the glucocorticoid-induced leucine zipper gene in dexamethasone-induced inhibition of mouse neutrophil migrationviacontrol of annexin A1 expression.
authors.affiliation: Pharmacology Section, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Ricci
authors.affiliation: Pharmacology Section, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Ronchetti
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.|Department of Diagnostic, Clinic, and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Pericolini
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gabrielli
authors.affiliation: Pharmacology Section, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cari
authors.affiliation: Pharmacology Section, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gentili
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Roselletti
authors.affiliation: Pharmacology Section, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Migliorati
authors.affiliation: Microbiology Section, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Vecchiarelli
authors.affiliation: Pharmacology Section, Department of Medicine, University of Perugia, Perugia, Italy; carlo.riccardi@unipg.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Riccardi
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D010538:Peritonitis / Q000139:chemically induced; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D017305:Annexin A1; D003907:Dexamethasone; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C498608:Dsip1 protein, mouse; C573274:annexin A1, mouse
keywords: inflammation; peritonitis; transcription