非离子表面活性剂囊泡通过抑制 NFκB 发挥抗炎作用。

IF 4.4 3区 医学 Q2 IMMUNOLOGY
Jonathan McGahon, Stuart Woods, Riccardo D'Elia, Craig W Roberts
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引用次数: 0

摘要

炎症可能是感染性和非感染性疾病的不良后果或致病原因。目前的抗炎药物存在一些缺陷,包括缺乏特异性和不良副作用。本文研究了由单棕榈醇甘油、磷酸二辛酯和胆固醇组成的非离子表面活性剂囊泡 (NISV) 作为抗炎药物的潜力及其作用模式。NISV 能够抑制 LPS 诱导的 BMD 巨噬细胞 IL-6。NISV 的单个成分--单棕榈醇甘油、磷酸二十六烷基酯和胆固醇并不影响 LPS 诱导的 IL-6 水平,这证明了 NISV 的配方对其抗炎作用至关重要。转录组分析表明,NISV 介导了 LPS 刺激巨噬细胞中炎症介质转录本的下调。值得注意的是,NISV 下调了 LPS 刺激巨噬细胞中的 NF-κB 转录本。通过细胞测量珠阵列对炎症介质的测量验证了一些转录组学发现,NISV 可抑制 LPS 诱导的 IL-6、IL-12 和多种趋化因子。进一步的研究表明,NISV 可抑制 Poly(I:C) 或 Pam3csk4 诱导的炎症介质。这表明 NISV 对 MyD88 和 TRIF 信号的影响是远端性的。总之,这些数据凸显了 NISV 作为抗炎疗法的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Non-ionic surfactant vesicles exert anti-inflammatory effects through inhibition of NFκB.

Inflammation can be an unwanted consequence or cause of debilitating diseases of infectious and non-infectious aetiologies. Current anti-inflammatory medications have several deficiencies including lack of specificity and undesirable side effects. Herein, the potential of non-ionic surfactant vesicles (NISV) comprised of monopalmityol glycerol, dicetyl phosphate and cholesterol) as an anti-inflammatory drug and their mode of action is investigated. NISV were able to inhibit LPS-induced IL-6 from BMD macrophages. The individual components of NISV, monopalmityol glycerol, dicetyl phosphate and cholesterol did not affect LPS induced IL-6 levels, proving that formulation of NISV is essential for their anti-inflammatory effects. Transcriptomic analyses showed NISV mediated down-regulation of transcripts for inflammatory mediators in LPS stimulated macrophages. Notably, NISV downregulate NF-κB transcripts in LPS stimulated macrophages. Measurement of inflammatory mediators by cytometric bead array validated a number of transcriptomic findings as NISV were found to inhibit LPS induced IL-6, IL-12, and multiple chemokines. Further investigation demonstrated that NISV inhibited Poly(I:C) or Pam3csk4 induced inflammatory mediators. This indicates that the effects of NISV are distal to both MyD88 and TRIF signalling. Overall, the data generated highlights the potential of NISV as an anti-inflammatory therapeutic.

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来源期刊
CiteScore
7.90
自引率
0.00%
发文量
18
审稿时长
>12 weeks
期刊介绍: Journal of Inflammation welcomes research submissions on all aspects of inflammation. The five classical symptoms of inflammation, namely redness (rubor), swelling (tumour), heat (calor), pain (dolor) and loss of function (functio laesa), are only part of the story. The term inflammation is taken to include the full range of underlying cellular and molecular mechanisms involved, not only in the production of the inflammatory responses but, more importantly in clinical terms, in the healing process as well. Thus the journal covers molecular, cellular, animal and clinical studies, and related aspects of pharmacology, such as anti-inflammatory drug development, trials and therapeutic developments. It also considers publication of negative findings. Journal of Inflammation aims to become the leading online journal on inflammation and, as online journals replace printed ones over the next decade, the main open access inflammation journal. Open access guarantees a larger audience, and thus impact, than any restricted access equivalent, and increasingly so, as the escalating costs of printed journals puts them outside University budgets. The unrestricted access to research findings in inflammation aids in promoting dynamic and productive dialogue between industrial and academic members of the inflammation research community, which plays such an important part in the development of future generations of anti-inflammatory therapies.
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