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Parthenium hysterophorus mediated inflammation and hyper‐responsiveness via NF‐κB pathway in human A549 lung cancer cell line
Environmental Toxicology ( IF 4.5 ) Pub Date : 2020-07-20 , DOI: 10.1002/tox.22989
Mandeep Kaur 1 , Kunj Bihari Gupta 2 , Shweta Thakur 3 , Sukhchain Kaur 2 , Monisha Dhiman 2
Affiliation  

Being one of the notorious weed P. hysterophorus has invaded almost every part India and is the lead cause of skin allergies and severe dermatitis among farmers and rural population. It is an invasive obnoxious weed capable of surviving extreme environmental conditions and various parts of this plant are reported to cause severe contact allergies in humans due to the presence of high concentrations of toxic sesquiterpene lactones viz. parthenin. It can stimulate numerous cellular and immune responses that may translate into Oxidative stress, allergies, and inflammation. The effect of P. hysterophorus flower extract was evaluated on cell viability, oxidative stress and inflammation in A549 lung cancer cell line by spectrophotometric and reverse transcriptase‐polymerase chain reaction methods. Schrodinger software based docking was performed for possible interactions studies. The A549 cells treated with P. hysterophorus flower extract favors increase in cell viability, reactive oxygen species generation. The mRNA expression of proinflammatory cytokines such as IFN‐γ, TNF‐α, and IL‐1β was significantly increased whereas no change in IL‐18 expression was observed. Significant increase in protein expression of NF‐κB was observed, suggesting the role of NF‐κB signalling in allergic responses. The docking studies demonstrated the potential interaction between Parthenin and NF‐κB/IL‐1β/IL‐18 suggesting their activation leading to inflammation. The current study emphasize that P. hysterophorus mediates oxidative stress, and inflammatory process via alterations in expression of proinflammatory cytokines such as IL‐1β, IFN‐γ through NF‐κB activation which was also confirmed in docking studies. Cellular and molecular mechanisms involved in pathogenesis of allergic/chronic inflammation and severe dermatitis need to be further investigated to identify specific binding partners responsible for severe inflammation which can provide some leads in developing effective targets against severe dermatitis and skin allergies.

中文翻译:

Parthenium hysterophorus 通过 NF-κB 通路介导人 A549 肺癌细胞系的炎症和高反应性

作为臭名昭著的杂草之一,P. hysterophorus 几乎侵入了印度的每一个地方,是农民和农村人口皮肤过敏和严重皮炎的主要原因。它是一种侵入性讨厌的杂草,能够在极端环境条件下生存,据报道,由于存在高浓度的有毒倍半萜内酯,该植物的各个部分会导致人类严重的接触过敏症。帕特宁。它可以刺激多种细胞和免疫反应,这些反应可能会转化为氧化应激、过敏和炎症。通过分光光度法和逆转录酶-聚合酶链反应方法评估了 P. hysterophorus 花提取物对 A549 肺癌细胞系细胞活力、氧化应激和炎症的影响。基于薛定谔软件的对接进行了可能的相互作用研究。用 P. hysterophorus 花提取物处理的 A549 细胞有利于增加细胞活力和活性氧的产生。促炎细胞因子如 IFN-γ、TNF-α 和 IL-1β 的 mRNA 表达显着增加,而 IL-18 表达没有变化。观察到 NF-κB 的蛋白质表达显着增加,表明 NF-κB 信号在过敏反应中的作用。对接研究证明了 Parthenin 和 NF-κB/IL-1β/IL-18 之间的潜在相互作用,表明它们的激活会导致炎症。目前的研究强调 P. hysterophorus 通过改变促炎细胞因子(如 IL-1β)的表达来介导氧化应激和炎症过程,IFN-γ 通过 NF-κB 激活,这也在对接研究中得到证实。需要进一步研究涉及过敏/慢性炎症和严重皮炎发病机制的细胞和分子机制,以确定导致严重炎症的特定结合伙伴,这可以为开发针对严重皮炎和皮肤过敏的有效靶标提供一些线索。
更新日期:2020-07-20
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