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Verteporfin inhibits lipopolysaccharide-induced inflammation by multiple functions in RAW 264.7 cells.
Toxicology and Applied Pharmacology ( IF 3.8 ) Pub Date : 2019-12-05 , DOI: 10.1016/j.taap.2019.114852
Yuting Wang 1 , Lei Wang 2 , James T F Wise 3 , Xianglin Shi 2 , Zhimin Chen 4
Affiliation  

Inflammation is a physiologic response to damage triggered by infection, injury or chemical irritation. Chronic inflammation produces repeated damage to cells and tissues, which can induce a variety of human diseases including cancer. Verteporfin, an FDA approved drug, is used for the treatment of age-related macular degeneration. The anti-tumor effects of verteporfin have been demonstrated by a number of studies. However, fewer studies focus on the anti-inflammatory functions of this drug. In this study, we investigated the anti-inflammatory effects and potential mechanisms of verteporfin. The classic lipopolysaccharide (LPS)-induced inflammation cell model was used. RAW 264.7 cells were pre-treated with verteporfin or vehicle control, followed by LPS stimulation. Verteporfin inhibited IL-6 and TNF-α at mRNA and protein expression levels. This effect was mediated through inhibition of the NF-κB and JAK/STAT pathways. Finally, verteporfin exhibited an anti-inflammation effect by crosslinking of protein such as NF-κB p65, JAK1, JAK2, STAT1, or STAT3 leading to inflammation. Taken together, these results indicate that verteporfin has the potential to be an effective therapeutic agent against inflammatory diseases.

中文翻译:

Verteporfin通过RAW 264.7细胞中的多种功能抑制脂多糖诱导的炎症。

炎症是对感染,伤害或化学刺激引起的损害的生理反应。慢性炎症会反复破坏细胞和组织,从而诱发多种人类疾病,包括癌症。Verteporfin是FDA批准的药物,用于治疗与年龄有关的黄斑变性。Verteporfin的抗肿瘤作用已通过许多研究证明。但是,很少有研究集中在这种药物的抗炎功能上。在这项研究中,我们研究了维替泊芬的抗炎作用及其潜在机制。使用经典的脂多糖(LPS)诱导的炎症细胞模型。RAW 264.7细胞用verteporfin或溶媒对照预处理,然后进行LPS刺激。韦替泊芬在mRNA和蛋白质表达水平抑制IL-6和TNF-α。这种作用是通过抑制NF-κB和JAK / STAT途径介导的。最后,维替泊芬通过交联导致发炎的蛋白质(例如NF-κBp65,JAK1,JAK2,STAT1或STAT3)而表现出抗炎作用。综上所述,这些结果表明维替泊芬具有作为抗炎性疾病的有效治疗剂的潜力。
更新日期:2019-12-05
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