Synthetic Glucocorticoid-Induced Leucine Zipper Peptide Inhibits Lipopolysaccharide-Induced Ocular Inflammation in Rats

Abstract

To demonstrate the anti-inflammatory action of a synthetic glucocorticoid-induced leucine zipper (GILZ 98-134) peptide (GILZ-p) in a model of endotoxin-induced uveitis (EIU) in rats. Methods: The EIU model was induced in Sprague Dawley rats with an intravitreal injection of lipopolysaccharide (LPS). Synthetic GILZ-p was injected intravitreally 6 h after the LPS injection. To evaluate the anti-inflammatory effects of GILZ-p, the inflammatory response in the anterior chamber and iris of the rat eyes was evaluated with a slitlamp microscope on days 0, 1, 2, 3, and 4 after GILZ-p injection. The retinal expression of inflammatory cytokines was measured on days 0, 1, 2, 3, and 4 after GILZ-p injection. Müller cell gliosis was also detected at planned time points after GILZ-p injection. Results: Anterior segment inflammation peaked at 24 h after LPS injection in the EIU model. Compared with the controls, intravitreal GILZ-p significantly suppressed LPS-induced anterior segment inflammation in the EIU rats. The levels of retinal inflammatory factors IL-1β, TNF-α, MCP-1, and ICAM-1 were simultaneously reduced by the intravitreal GILZ-p injection. The expression of vimentin in the EIU retina was significantly reduced by GILZ-p, and the downregulated aquaporin 4 in the EIU retina was significantly restored by GILZ-p. Conclusion: The synthetic GILZ-p inhibited the inflammatory reaction in the EIU model and may have utility in the treatment of inflammatory ocular disease.

Glucocorticoid-Induced Leucine Zipper-Mediated TLR2 Downregulation Accounts for Reduced Neutrophil Activity Following Acute DEX Treatment

“…Glucocorticoid-induced leucine zipper (GILZ) is a gene rapidly transcribed by either endogenous or pharmacologically administered glucocorticoids [ 1 , 2 , 3 , 4 , 5 ]. Several studies have demonstrated that GILZ exerts anti-inflammatory activity, often acting as a mediator of glucocorticoid actions but without the glucocorticoid-derived side effects [ 6 , 7 , 8 , 9 , 10 ]. While almost ubiquitously expressed, GILZ is rapidly induced by glucocorticoids primarily in immune cells of the adaptive and innate system and regulates their cellular functions (e.g., activation, differentiation, and apoptosis) [ 3 , 11 , 12 , 13 , 14 , 15 , 16 ].…”

A Glance at the Use of Glucocorticoids in Rare Inflammatory and Autoimmune Diseases: Still an Indispensable Pharmacological Tool?

“…Another proof of the efficacy of GILZ-based peptides is given by the use of a synthetic TAT-GILZ peptide (GILZ-p) in a model of ocular uveitis in rats. The inflammatory response was counteracted by the intravitreal injection of GILZ-p, which could reduce the expression of IL-1β and TNF-α ( 86 ).…”

Pranoprofen Nanoparticles With Poly(L-Lactide)-b-Poly(Ethylene Glycol)-b-Poly(L-Lactide) as the Matrix Toward Improving Ocular Anti-inflammation

“…The animal model with infected eyes was set up by an injection of LPS/PS solution (0.2 mg/ml) into the anterior chamber (Guo et al, 2019). The incision was made in the cornea margin of rabbits to allow the aqueous humor to flow naturally.…”