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.

中文翻译：

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木犀草素通过抑制 NF-κB 和 MAPK 通路减弱 IL-1β 诱导的 THP-1 对 ARPE-19 细胞的粘附

细胞因子诱导的内皮功能障碍导致视网膜色素上皮 (RPE) 细胞中的炎症和血管粘附分子的产生。炎症是视网膜变性 (RD) 疾病的关键介质，包括与年龄相关的黄斑变性 (AMD)，并且可以通过 RPE 细胞中的抗炎活性来预防 RD 进展。黄酮类多酚木犀草素 (LU) 具有抗炎和抗糖尿病活性，但其对视网膜保护的作用尚不清楚。在这里，我们检查了木犀草素减轻细胞因子引发的 APPE-19 细胞中与 RD 相关的炎症标志物的能力。我们发现木犀草素降低了白细胞介素- (IL-) 6、IL-8、可溶性细胞间粘附分子-1 (sICAM-1)、β-刺激的 ARPE-19 细胞。木犀草素还增加了抗炎蛋白血红素加氧酶-1 (HO-1) 的水平。有趣的是，木犀草素诱导蛋白激酶 B (AKT) 磷酸化，从而抑制核因子 - (NF-) κ B 从细胞质转移到细胞核并抑制丝裂原活化蛋白激酶 (MAPK) 炎症途径。此外，与 MAPK 抑制剂和木犀草素共同治疗降低了炎性细胞因子和趋化因子水平，并进一步抑制了 THP-1 粘附。总的来说，这些结果提供了证据表明木犀草素通过阻断 MAPK 和 NF- κ的激活来保护 ARPE-19 细胞免受 IL-1 β刺激的 IL-6、IL-8、sICAM-1 和 MCP-1 产生的增加B 信号通路，从而改善炎症反应。