Feng Ting-Ting, Liang Ze-Yu, Chen Song
Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Medical University Tianjin 300020, China.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9126-32. eCollection 2015.
Dysfunction of the retinal pigment epithelium (RPE) resulting from chronic inflammation is implicated in the pathogenesis of age-related macular degeneration (AMD). It has been reported that tumor necrosis factor-α (TNF-α) could induce intercellular adhesion molecule-1 (ICAM-1) expression in RPE cells. FLZ, a novel synthetic squamosamide derivative from a Chinese herb, Annona glabra, has displayed significant anti-inflammatory activity. However, the effects of FLZ on TNF-α-induced ICAM-1 expression in RPE cells remain unknown. Therefore, in the present study, we evaluated the effects of FLZ on TNF-α-induced ICAM-1 expression in RPE cells. We found that FLZ prevented TNF-α-induced ICAM-1 expression and the ability of monocytes to adhere to ARPE-19 cells induced by TNF-α. Furthermore, FLZ inhibited TNF-α-induced NF-κB p65 expression, as well as phosphorylation of IκBα in ARPE-19 cells. Taken together, these results suggest that FLZ inhibited TNF-α-induced ICAM-1 expression through blocking NF-κB signaling pathway in ARPE-19 cells. Thus, FLZ could be used for designing novel therapeutic agents against AMD.
慢性炎症导致的视网膜色素上皮（RPE）功能障碍与年龄相关性黄斑变性（AMD）的发病机制有关。据报道，肿瘤坏死因子-α（TNF-α）可诱导RPE细胞中细胞间黏附分子-1（ICAM-1）的表达。FLZ是一种源自中草药光叶番荔枝的新型合成番荔枝酰胺衍生物，已显示出显著的抗炎活性。然而，FLZ对TNF-α诱导的RPE细胞中ICAM-1表达的影响尚不清楚。因此，在本研究中，我们评估了FLZ对TNF-α诱导的RPE细胞中ICAM-1表达的影响。我们发现FLZ可阻止TNF-α诱导的ICAM-1表达以及TNF-α诱导的单核细胞黏附于ARPE-19细胞的能力。此外，FLZ抑制了TNF-α诱导的ARPE-19细胞中NF-κB p65的表达以及IκBα的磷酸化。综上所述，这些结果表明FLZ通过阻断ARPE-19细胞中的NF-κB信号通路抑制了TNF-α诱导的ICAM-1表达。因此，FLZ可用于设计针对AMD的新型治疗药物。
