Esculetin Protects Human Retinal Pigment Epithelial Cells from Lipopolysaccharide-induced Inflammation and Cell Death
Küçük Resim Yok
Tarih
2018
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Taylor & Francis Inc
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Purpose: Age-related macular degeneration (AMD) is the most common cause of visual loss. The dry AMD is characterized by retinal pigment epithelium (RPE) death and changes in AMD lead to severe loss of vision. Coumarin-derived esculetin has a number of therapeutic and pharmacological effects such as anti-inflammatory and antioxidant with various mechanisms. The purpose of this study was to investigate the effects of esculetin treatment on lipopolysaccharide (LPS)-induced inflammation, oxidative stress, and cell survival.Material and methods: Human RPE cells (ARPE-19) were incubated for 24-72h with 5g/ml LPS to induce inflammation and oxidative stress. Esculetin (5 M) was used to protect the cells from LPS-induced damage. The cell viability was evaluated by quantitative 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. Interleukin 6 (IL-6), IL-12, and vascular endothelial growth factor (VEGF) levels were determined by enzyme-linked immunosorbent assay (ELISA). IL-1, tumor necrosis factor receptor (TNFR), TNF-related apoptosis-inducing ligand (TRAIL), catalase, glutathione peroxidase (GPx), superoxide dismutase 1 (CuZnSOD) and SOD2 (MnSOD) mRNA expressions were analyzed by RT-quantitative polymerase chain reaction. Apoptosis was monitored by cell-based cytometer. NF-kappa B (NF-B) p65/RelA levels were determined by ELISA, and NF-B protein expression and extracellular signal-regulated kinase (ERK1/2) phosphorylation were evaluated by Western blot analysis.Results: Esculetin treatment significantly suppressed LPS-induced cell death mediated by apoptosis and necrosis in a concentration-dependent manner. While LPS caused significant inflammation with cytokine increase in cells, esculetin reduced the expression of LPS-induced cytokines, VEGF, TNFR, and TRAIL. Furthermore, exposure to LPS increased the expression of GPx and mitochondrial MnSOD, leading to oxidative stress in the cells. Esculetin treatment attenuated phosphorylation of ERK1/2 and NF-B expression mediated by LPS.Conclusions: These results suggest that esculetin may be an alternative treatment option for endotoxin-induced inflammation and oxidative stress, which therefore may inhibit the development of LPS-mediated AMD.
Açıklama
Anahtar Kelimeler
Esculetin, ARPE-19 Cells, Age-Related Macular Degeneration, Inflammation, Lipopolysaccharide, Macular Degeneration, Oxidative Stress, Hydrogen-Peroxide, Diabetic-Rats, Expression, Activation, Pathway, Induction, Cytokines, Vegf
Kaynak
Current Eye Research
WoS Q Değeri
Q3
Scopus Q Değeri
Q2
Cilt
43
Sayı
9
