New insights into NLRP3 within inflammatory disease

NLRP3 在炎症性疾病中的新见解

• 批准号: MR/T016515/1
• 负责人: David Brough
• 金额: $ 190.62万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT016515%2F1
• 关键词: New; insights; into; NLRP3; within

Inflammation is our bodies' response to infection and injury. Characterised by redness, swelling, and heat, an inflammatory response involves the movement of cells from the bloodstream to an infected or injured tissue or organ. Typically inflammation is a beneficial response. However, a failure to switch off an inflammatory response, or for it to clear away fully (or resolve), can lead to chronic or inappropriate inflammation. This can result in the death of healthy cells and tissue. As we get older the bodies' control of how it regulates inflammation starts to decline. During disease our control of inflammation is also compromised. When inflammation is not regulated appropriately it starts to become a cause of disease, or makes disease outcomes worse. Thus we need to understand the mechanisms regulating inflammation, and then we need to develop ways of blocking it during disease. By combining the expertise of scientists from different fields I aim to make a leap forward in how we understand a particularly damaging inflammatory response. Working with experts on cell function and biology I will conduct a programme of research that aims to understand a) how damaging inflammation is switched on, and b) how damaging inflammation can be switched off. Only through an improved understanding of these processes can we then target inflammation in disease effectively.

炎症是我们的身体对感染和损伤的反应。炎症反应以发红、肿胀和发热为特征，涉及细胞从血流到受感染或受伤的组织或器官的运动。通常，炎症是一种有益的反应。然而，未能关闭炎症反应，或完全清除(或消除)，可能会导致慢性或不适当的炎症。这可能会导致健康细胞和组织的死亡。随着年龄的增长，身体对炎症调节方式的控制力开始减弱。在疾病期间，我们对炎症的控制也受到了影响。当炎症没有得到适当的调控时，它开始成为疾病的原因，或者使疾病结果变得更糟。因此，我们需要了解炎症的调节机制，然后我们需要开发在疾病期间阻止炎症的方法。通过结合来自不同领域的科学家的专业知识，我的目标是在我们如何理解一种特别具有破坏性的炎症反应方面取得飞跃。我将与细胞功能和生物学方面的专家合作，进行一项研究计划，旨在了解a)如何启动破坏性炎症，以及b)如何关闭破坏性炎症。只有通过对这些过程的更好理解，我们才能有效地针对疾病中的炎症。

项目成果

The two pore potassium channel THIK-1 regulates NLRP3 inflammasome activation.

• DOI: 10.1002/glia.24174
• 发表时间: 2022-07
• 期刊: Glia
• 影响因子: 6.2

The comparable tumour microenvironment in sporadic and NF2-related schwannomatosis vestibular schwannoma.

• DOI: 10.1093/braincomms/fcad197
• 发表时间: 2023
• 期刊: Brain communications
• 影响因子: 4.8

Mechanisms of NLRP3 priming in inflammaging and age related diseases.

• DOI: 10.1016/j.cytogfr.2020.08.003
• 发表时间: 2020-10
• 期刊: Cytokine & growth factor reviews
• 影响因子: 13
• 作者: Gritsenko A;Green JP;Brough D;Lopez-Castejon G
• 通讯作者: Lopez-Castejon G

Inhibiting the NLRP3 Inflammasome.

• DOI: 10.3390/molecules25235533
• 发表时间: 2020-11-25
• 期刊: Molecules (Basel, Switzerland)
• 作者: El-Sharkawy LY;Brough D;Freeman S
• 通讯作者: Freeman S

LRRC8A is essential for hypotonicity-, but not for DAMP-induced NLRP3 inflammasome activation.

LRRC8A对于低注度性至关重要，但对于潮湿诱导的NLRP3炎性体激活不是必不可少的。

• DOI: 10.7554/elife.59704
• 发表时间: 2020-11-20
• 期刊: eLife
• 影响因子: 7.7
• 作者: Green JP;Swanton T;Morris LV;El-Sharkawy LY;Cook J;Yu S;Beswick J;Adamson AD;Humphreys NE;Bryce R;Freeman S;Lawrence C;Brough D
• 通讯作者: Brough D