Parasaram Vaideesh, Nosoudi Nasim, Chowdhury Aniqa, Vyavahare Naren
Department of Bioengineering, Clemson University, SC, United States.
Department of Biomedical, Industrial and Human Factors Engineering, Wright State University, OH, United States.
Biochem Biophys Res Commun. 2018 Apr 30;499(1):24-29. doi: 10.1016/j.bbrc.2018.03.100. Epub 2018 Mar 19.
Emphysema is characterized by degradation of lung alveoli that leads to poor airflow in lungs. Irreversible elastic fiber degradation by matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) activity leads to loss of elasticity and drives the progression of this disease. We investigated if a polyphenol, pentagalloyl glucose (PGG) can increase elastin production in pulmonary fibroblasts. We also studied the effect of PGG treatment in reducing MMP activity and ROS levels in cells. We exposed rat pulmonary fibroblasts to two different types of inflammatory environments i.e., tumor necrosis factor-α (TNF-α) and cigarette smoke extract (CSE) to mimic the disease. Parameters like lysyl oxidase (LOX) and elastin gene expression, MMP-9 activity in the medium, lysyl oxidase (LOX) activity and ROS levels were studied to assess the effect of PGG on pulmonary fibroblasts. CSE inhibited lysyl oxidase (LOX) enzyme activity that resulted in a decreased elastin formation. Similarly, TNF-α treated cells showed less elastin in the cell layers. Both these agents caused increase in MMP activity and ROS levels in cells. However, when supplemented with PGG treatment along with these two inflammatory agents, we saw a significant increase in elastin deposition, reduction in both MMP activity and ROS levels. Thus PGG, which has anti-inflammatory, anti-oxidant properties coupled with its ability to aid in elastic fiber formation, can be a multifunctional drug to potentially arrest the progression of emphysema.
肺气肿的特征是肺泡退化,导致肺部气流不畅。基质金属蛋白酶(MMPs)和活性氧(ROS)活性引起的不可逆弹性纤维降解会导致弹性丧失,并推动该疾病的发展。我们研究了一种多酚——五倍子酰葡萄糖(PGG)是否能增加肺成纤维细胞中弹性蛋白的产生。我们还研究了PGG处理对降低细胞中MMP活性和ROS水平的影响。我们将大鼠肺成纤维细胞暴露于两种不同类型的炎症环境中,即肿瘤坏死因子-α(TNF-α)和香烟烟雾提取物(CSE),以模拟该疾病。研究了诸如赖氨酰氧化酶(LOX)和弹性蛋白基因表达、培养基中MMP-9活性、赖氨酰氧化酶(LOX)活性和ROS水平等参数,以评估PGG对肺成纤维细胞的影响。CSE抑制了赖氨酰氧化酶(LOX)的酶活性,导致弹性蛋白形成减少。同样,经TNF-α处理的细胞在细胞层中显示出较少的弹性蛋白。这两种物质都导致细胞中MMP活性和ROS水平升高。然而,当在这两种炎症介质处理的同时补充PGG时,我们发现弹性蛋白沉积显著增加,MMP活性和ROS水平均降低。因此,具有抗炎、抗氧化特性以及有助于弹性纤维形成能力的PGG,可能是一种潜在的多功能药物,可阻止肺气肿的进展。