Effects of PPAR-γ and RXR-α on mouse meibomian gland epithelial cells during inflammation induced by latanoprost. (November 2022)

• Record Type: Journal Article
• Authors: Jiang, Xiu-ying; Yang, Ping-sun; Xiao, Ou; Yu, Kang; Wang, Shu-yi; Yang, Shuang-Jian; Zhou, Shi-you
• Is Part Of: Experimental eye research. Volume 224(2022)
• Publication Date: 2022-11
• Subjects: Latanoprost -- PPAR-γ and RXR-α -- Inflammation -- Meibomian gland -- Differentiation; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2022.109251
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: The purpose of this study is to investigate the effects of latanoprost on the secretion of cytokines and chemokines from meibomian gland epithelial cells, and to evaluate the modulation of peroxisome proliferator-activated receptor γ (PPAR-γ) and retinoid X receptor α (RXR-α) during latanoprost-induced inflammation. Mouse meibomian gland epithelial cells were cultured in proliferation and differentiation medium, respectively. Cells were exposed to latanoprost, rosiglitazone (PPAR-γ agonist), or LG100268 (RXR-α agonist), respectively. The expression of IL−6, IL-1β, TNF-α, MMP-9, MCP-1, and CCL-5 were detected by real-time PCR and ELISA. The effect of latanoprost, rosiglitazone, LG100268, and inflammatory cytokines on the differentiation of meibocyte were evaluated by related gene expression and lipid staining. The expression of Keratin-1, 6, 17 protein was detected by western immunoblotting. The results showed that the above cytokines could be induced by latanoprost in meibomian gland epithelial cells. LG100268 and rosiglitazone could inhibit the production of IL-6 and TNF-α induced by latanoprost, respectively. Latanoprost suppressed the expression of differentiation-related mRNA through a positive feedback loop by enhancement of COX-2 expression via FP receptor-activated ERK signaling. The expression of Keratin-17 was upregulated by rosiglitazone and suppressed by LG100268. The application of IL-6 and TNF-α showed negative effects on lipid accumulation in meibomian gland epithelial cells. These results demonstrated that latanoprost could induce inflammation and suppress differentiation of mouse meibomian gland epithelial cells. The activation of PPAR-γ and RXR-α showed an anti-inflammatory effect, showing a potential role to antagonize the effect of latanoprost eyedrops on meibomian gland epithelial cells. Highlights: Latanoprost increased the secretion of cytokines, chemokines in meibomian gland epithelial cells. The secretion levels of cytokine and chemokine were significantly higher in meibomian gland cells under differentiation medium. Latanoprost enhances the expression of COX-2 through ERK signaling via FP receptor in meibomian gland epithelial cells. The activation of either PPAR-γ or RXR-α suppressed the secretion of cytokines induced by latanoprost in meibomian gland epithelial cells. The application of IL-6 and TNF-α showed negative effects on lipid accumulation in meibomian gland epithelial cells.