Abstract
Cytokine-induced endothelial dysfunction leads to inflammation and vascular adhesion molecule production in retinal pigment epithelium (RPE) cells. Inflammation is a critical mediator in retinal degeneration (RD) diseases, including age-related macular degeneration (AMD), and RD progression may be prevented through anti-inflammatory activity in RPE cells. The flavonoid polyphenol luteolin (LU) has anti-inflammatory and antidiabetes activities, but its effects regarding retinal protection remain unknown. Here, we examined the ability of luteolin to alleviate markers of inflammation related to RD in cytokine-primed APPE-19 cells. We found that luteolin decreased the levels of interleukin- (IL-) 6, IL-8, soluble intercellular adhesion molecule-1 (sICAM-1), and monocyte chemoattractant protein-1 (MCP-1) and attenuated adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. Luteolin also increased anti-inflammatory protein heme oxygenase-1 (HO-1) levels. Interestingly, luteolin induced protein kinase B (AKT) phosphorylation, thus inhibiting nuclear factor- (NF-) κB transfer from cytoplasm into the nucleus and suppressing mitogen-activated protein kinase (MAPK) inflammatory pathways. Furthermore, cotreatment with MAPK inhibitors and luteolin decreased inflammatory cytokine and chemokine levels, and further suppressed THP-1 adhesion. Overall, these results provide evidence that luteolin protects ARPE-19 cells from IL-1β-stimulated increases of IL-6, IL-8, sICAM-1, and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways, thus ameliorating the inflammatory response.
Highlights
The retinal pigment epithelium (RPE) is a single layer of pigment cells, which is in close contact with photoreceptors and maintains visual function [1]
Luteolin concentrations of ≤50 μM showed no significant cytotoxicity in ARPE-19 cells, while cell numbers were significantly reduced at concentrations of ≥100 μM (Figure 2(a))
Our results showed that luteolin at ≥1 μM enhanced the expression of phosphorylated AKT proteins in IL-1β-stimulated ARPE19 cells compared with in cells treated with IL-1β alone (Figures 2(f) and 2(g))
Summary
The retinal pigment epithelium (RPE) is a single layer of pigment cells, which is in close contact with photoreceptors and maintains visual function [1]. Inflammation clearly plays a role in the development of age-related macular degeneration (AMD), which is a cause of severe irreversible visual impairment in elderly persons and in diabetic retinopathy [2, 3]. A. Mediators of Inflammation variety of factors promote retinal tissue degeneration and AMD progression, including genetic and environmental factors, aging, and oxidative stress [4]. AMD involves reduced photoreceptor cells and retinal pigment epithelium dysfunction in the macula and can be classified as “dry AMD” or “wet/exudative/neovascular AMD.”. Compared to neovascular AMD, dry AMD has a higher incidence, but involves less vision degradation and is less frequently a cause of “blindness” [5, 6]. Dry AMD can potentially evolve into neovascular AMD, leading to irreversible vision loss [7, 8]. The best means of avoiding vision deterioration in elderly persons and cases of diabetic retinopathy is to prevent macular degeneration
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