title: Glucocorticoid-induced leucine zipper overexpression inhibits lipopolysaccharide-induced retinal inflammation in rats.
abstract: Glucocorticoid-induced leucine zipper (GILZ) mediates several effects of glucocorticoids and has important anti-inflammatory properties. Here, we explored the role of GILZ in inhibiting retinal inflammation. Endotoxin-induced uveitis (EIU) was established in rats by intravitreal injection of lipopolysaccharide (LPS). GILZ levels decreased in the EIU retina after LPS injection. Retinal GILZ was downregulated by recombinant lentivirus-delivered short-hairpin RNA targeting GILZ (shRNA-GILZ-rLV) and upregulated by recombinant lentivirus-mediated GILZ overexpression (Oe-GILZ-rLV). GILZ silencing attenuated the anti-inflammatory effects of intravitreal injection of triamcinolone acetonide (TA) in the EIU retina, as demonstrated by increased retinal interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1and intercellular cell adhesion molecule-1 expression at 18 h after TA injection. A Bio-Plex cytokine assay and western blotting demonstrated that GILZ overexpression inhibited the effects of LPS, downregulating retinal IL-1β, MCP-1, MIP-1α, and IL-17 and inhibiting LPS-induced activation of the retinal toll-like receptor 4-myeloid differentiation factor 88 signaling pathway. At 48 and 72 h after LPS injection, the clinical score of inflammation was significantly lower in Oe-GILZ-rLV-transfected eyes than in blank-rLV-transfected eyes. Histological examination showed a 67.85% reduction of infiltrating inflammatory cells in the anterior chamber and a 58.97% reduction in vitreous cavity of Oe-GILZ-rLV transfected eyes at 48 h after LPS injection. Taken together, our results suggest that GILZ is a novel therapeutic target for the treatment of retinal inflammatory diseases.
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China. Electronic address: ruibeegu@163.com.
authors.forename: Ruiping
authors.initials: R
authors.lastname: Gu
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China. Electronic address: boyaray@126.com.
authors.forename: Boya
authors.initials: B
authors.lastname: Lei
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China. Electronic address: 13674092@qq.com.
authors.forename: Qinmeng
authors.initials: Q
authors.lastname: Shu
authors.affiliation: Research Center, Eye and ENT Hospital of Fudan University, Shanghai 200031, China. Electronic address: ligang490523@126.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China. Electronic address: xugezhi@sohu.com.
authors.forename: Gezhi
authors.initials: G
authors.lastname: Xu
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D010211:Papilledema / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014605:Uveitis / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D014157:Transcription Factors; C498609:Tsc22d3 protein, rat
keywords: Anterior segment inflammation; Cytokine; Endotoxin-induced uveitis; Glucocorticoid-induced leucine zipper; Lipopolysaccharide