The Inhibitory Role of M2000 (β-D-Mannuronic Acid) on Expression of Toll-like Receptor 2 and 4 in HT29 Cell Line.

IF 4.2 Q3 Pharmacology, Toxicology and Pharmaceutics Recent patents on inflammation & allergy drug discovery Pub Date : 2019-01-01 DOI:10.2174/1872213X13666181211160238
Laleh Sharifi, Mona Moshiri, Mohammad M S Dallal, Mohammad H Asgardoon, Maryam Nourizadeh, Saied Bokaie, Abbas Mirshafiey
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引用次数: 2

Abstract

Background/objectives: Anti-inflammatory agents play a crucial role in controlling inflammatory diseases such as Inflammatory Bowel Disease (IBD) but their use is restricted due to their vast side effects. M2000 (β-D-mannuronic acid) is a new immunomodulatory drug. According to the capacity of M2000 in suppressing some molecules involved in Toll Like Receptors (TLRs) signaling and reducing oxidative stress we hypothesize that, this molecule may have a potential role in decreasing inflammatory responses in IBD. The aim of this study was to evaluate the cytotoxicity of M2000 and its effect on the gene expression of TLR2 and TLR4.

Methods: HEK293 cell line was grown and divided into 96-well cell plate and MTT assay was performed. HT29 cells were cultured and treated with low and high doses of M2000. Total RNA was extracted and cDNA synthesized and quantitative real-time PCR was done to quantify the TLR2 and TLR4 mRNA expression.

Results: We found that M2000 at the concentration of ≤ 1000µg/ml had no obvious cytotoxicity effect on the HEK293 cells. Also, low and high doses of M2000 could significantly down-regulate both TLR2 and TLR4 mRNA expression. Moreover, a significant reduction in gene expression of TLR2 and TLR4 in an inflammatory condition resulted in high doses of M2000 in the presence of LPS.

Conclusion: Our study which was conducted in colonic epithelial cell model, shows that M2000 can be considered as a new anti-inflammatory agent in IBD. However, more comprehensive experimental and clinical studies are required to recognize the molecular mechanism of M2000 and also its safety and efficacy.

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M2000对HT29细胞Toll样受体2和4表达的抑制作用。
背景/目的:抗炎药在控制炎症性肠病(IBD)等炎症性疾病方面发挥着至关重要的作用,但由于其巨大的副作用,其使用受到限制。M2000(β-D-甘露糖醛酸)是一种新型的免疫调节药物。根据M2000在抑制Toll样受体(TLRs)信号传导和减少氧化应激中的一些分子方面的能力,我们假设该分子可能在减少IBD的炎症反应中发挥潜在作用。本研究旨在评价M2000的细胞毒性及其对TLR2和TLR4基因表达的影响。培养HT29细胞并用低剂量和高剂量的M2000处理。提取总RNA并合成cDNA,并进行定量实时PCR以定量TLR2和TLR4的mRNA表达。结果:M2000在≤1000µg/ml浓度下对HEK293细胞无明显的细胞毒性作用。此外,低剂量和高剂量的M2000可以显著下调TLR2和TLR4 mRNA的表达。此外,炎症条件下TLR2和TLR4基因表达的显著降低导致在LPS存在下高剂量的M2000。结论:我们在结肠上皮细胞模型中进行的研究表明,M2000可以被认为是一种新的IBD抗炎剂。然而,需要更全面的实验和临床研究来认识M2000的分子机制及其安全性和有效性。
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期刊介绍: Recent Patents on Inflammation & Allergy Drug Discovery publishes review articles by experts on recent patents in the field of inflammation and allergy drug discovery e.g. on novel bioactive compounds, analogs and targets. A selection of important and recent patents in the field is also included in the journal. The journal is essential reading for all researchers involved in inflammation and allergy drug design and discovery.
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