• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

RIPK1 抑制通过抑制破骨细胞生成来减轻实验性自身免疫性关节炎。

RIPK1 inhibition attenuates experimental autoimmune arthritis via suppression of osteoclastogenesis.

机构信息

The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.

Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.

出版信息

J Transl Med. 2019 Mar 15;17(1):84. doi: 10.1186/s12967-019-1809-3.

DOI:10.1186/s12967-019-1809-3
PMID:30876479
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6419814/
Abstract

BACKGROUND

Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease characterized by upregulation of inflammatory cell death and osteoclastogenesis. Necrostatin (NST)-1s is a chemical inhibitor of receptor-interacting serine/threonine-protein kinase (RIPK)1, which plays a role in necroptosis.

METHODS

We investigated whether NST-1s decreases inflammatory cell death and inflammatory responses in a mouse model of collagen-induced arthritis (CIA).

RESULTS

NST-1s decreased the progression of CIA and the synovial expression of proinflammatory cytokines. Moreover, NST-1s treatment decreased the expression of necroptosis mediators such as RIPK1, RIPK3, and mixed lineage kinase domain-like (MLKL). In addition, NST-1s decreased osteoclastogenesis in vitro and in vivo. NST-1s downregulated T helper (Th)1 and Th17 cell expression, but promoted Th2 and regulatory T (Treg) cell expression in CIA mice.

CONCLUSIONS

These results suggest that NST-1s attenuates CIA progression via the inhibition of osteoclastogenesis and might be a potential therapeutic agent for RA therapy.

摘要

背景

类风湿性关节炎（RA）是一种慢性全身性炎症性疾病，其特征是炎症细胞死亡和破骨细胞生成的上调。Necrostatin-1s（NST-1s）是受体相互作用丝氨酸/苏氨酸蛋白激酶（RIPK）1 的化学抑制剂，在细胞程序性坏死中发挥作用。

方法

我们研究了 NST-1s 是否可以减少胶原诱导性关节炎（CIA）小鼠模型中的炎症细胞死亡和炎症反应。

结果

NST-1s 可降低 CIA 的进展和滑膜中促炎细胞因子的表达。此外，NST-1s 治疗可降低程序性坏死介质如 RIPK1、RIPK3 和混合谱系激酶结构域样（MLKL）的表达。此外，NST-1s 可减少体外和体内的破骨细胞生成。NST-1s 下调 CIA 小鼠中的辅助性 T（Th）1 和 Th17 细胞表达，但促进 Th2 和调节性 T（Treg）细胞表达。

结论

这些结果表明，NST-1s 通过抑制破骨细胞生成来减轻 CIA 的进展，可能是 RA 治疗的潜在治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ca/6419814/c9378ba626f7/12967_2019_1809_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ca/6419814/2d6957caddc8/12967_2019_1809_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ca/6419814/510f7647df64/12967_2019_1809_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ca/6419814/91aab95c7b48/12967_2019_1809_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ca/6419814/643f7e82aa2f/12967_2019_1809_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ca/6419814/c9378ba626f7/12967_2019_1809_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ca/6419814/2d6957caddc8/12967_2019_1809_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ca/6419814/510f7647df64/12967_2019_1809_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ca/6419814/91aab95c7b48/12967_2019_1809_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ca/6419814/643f7e82aa2f/12967_2019_1809_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ca/6419814/c9378ba626f7/12967_2019_1809_Fig5_HTML.jpg

相似文献

1
RIPK1 inhibition attenuates experimental autoimmune arthritis via suppression of osteoclastogenesis.RIPK1 抑制通过抑制破骨细胞生成来减轻实验性自身免疫性关节炎。
J Transl Med. 2019 Mar 15;17(1):84. doi: 10.1186/s12967-019-1809-3.
2
Inhibition of keratinocyte necroptosis mediated by RIPK1/RIPK3/MLKL provides a protective effect against psoriatic inflammation.抑制角质形成细胞坏死性凋亡介导的 RIPK1/RIPK3/MLKL 对银屑病炎症具有保护作用。
Cell Death Dis. 2020 Feb 19;11(2):134. doi: 10.1038/s41419-020-2328-0.
3
Interferon-gamma regulates inflammatory cell death by targeting necroptosis in experimental autoimmune arthritis.干扰素-γ通过靶向实验性自身免疫性关节炎中的坏死性凋亡来调节炎症细胞死亡。
Sci Rep. 2017 Aug 31;7(1):10133. doi: 10.1038/s41598-017-09767-0.
4
KW2449 ameliorates collagen-induced arthritis by inhibiting RIPK1-dependent necroptosis.KW2449 通过抑制 RIPK1 依赖性细胞坏死来改善胶原诱导性关节炎。
Front Immunol. 2023 Mar 13;14:1135014. doi: 10.3389/fimmu.2023.1135014. eCollection 2023.
5
Targeting of Phospholipase D1 Ameliorates Collagen-Induced Arthritis via Modulation of Treg and Th17 Cell Imbalance and Suppression of Osteoclastogenesis.靶向磷脂酶 D1 通过调节 Treg 和 Th17 细胞失衡和抑制破骨细胞生成来改善胶原诱导性关节炎。
Int J Mol Sci. 2020 May 2;21(9):3230. doi: 10.3390/ijms21093230.
6
The neurotoxicant PCB-95 by increasing the neuronal transcriptional repressor REST down-regulates caspase-8 and increases Ripk1, Ripk3 and MLKL expression determining necroptotic neuronal death.神经毒性物质 PCB-95 通过增加神经元转录抑制因子 REST，下调半胱天冬酶-8，并增加 Ripk1、Ripk3 和 MLKL 的表达，从而导致坏死性神经元死亡。
Biochem Pharmacol. 2017 Oct 15;142:229-241. doi: 10.1016/j.bcp.2017.06.135. Epub 2017 Jul 1.
7
The antibody atliximab attenuates collagen-induced arthritis by neutralizing AIMP1, an inflammatory cytokine that enhances osteoclastogenesis.阿昔单抗抗体通过中和 AIMP1 来减轻胶原诱导性关节炎，AIMP1 是一种增强破骨细胞生成的炎症细胞因子。
Biomaterials. 2015 Mar;44:45-54. doi: 10.1016/j.biomaterials.2014.12.017. Epub 2015 Jan 12.
8
RIPK1 can function as an inhibitor rather than an initiator of RIPK3-dependent necroptosis.RIPK1 可以作为 RIPK3 依赖性细胞坏死的抑制剂，而不是起始因子。
FEBS J. 2014 Nov;281(21):4921-34. doi: 10.1111/febs.13034. Epub 2014 Oct 4.
9
TWEAK and RIPK1 mediate a second wave of cell death during AKI.TWEAK 和 RIPK1 在 AKI 期间介导第二波细胞死亡。
Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):4182-4187. doi: 10.1073/pnas.1716578115. Epub 2018 Mar 27.
10
Tetrandrine ameliorates collagen-induced arthritis in mice by restoring the balance between Th17 and Treg cells via the aryl hydrocarbon receptor.汉防己甲素通过芳烃受体恢复Th17细胞与调节性T细胞之间的平衡，从而改善小鼠胶原诱导的关节炎。
Biochem Pharmacol. 2016 Feb 1;101:87-99. doi: 10.1016/j.bcp.2015.11.025. Epub 2015 Nov 27.

引用本文的文献

1
Steamed panax notoginseng mitigates CA-MRSA USA300-induced necroptosis in human neutrophils.蒸制三七减轻耐甲氧西林金黄色葡萄球菌USA300诱导的人中性粒细胞坏死性凋亡。
Front Pharmacol. 2025 May 30;16:1546652. doi: 10.3389/fphar.2025.1546652. eCollection 2025.
2
Structure-based design of potent and selective inhibitors targeting RIPK3 for eliminating on-target toxicity in vitro.基于结构设计强效且选择性的RIPK3抑制剂以消除体外脱靶毒性
Nat Commun. 2025 May 8;16(1):4288. doi: 10.1038/s41467-025-59432-8.
3
The Involvement of RIPK1 in Alopecia Areata.

本文引用的文献

1
Necrostatin-7 suppresses RANK-NFATc1 signaling and attenuates macrophage to osteoclast differentiation.Necrostatin-7 抑制 RANK-NFATc1 信号通路并减弱巨噬细胞向破骨细胞的分化。
Biochem Biophys Res Commun. 2018 Sep 5;503(2):544-549. doi: 10.1016/j.bbrc.2018.05.153. Epub 2018 Jul 7.
2
Necrostatin-1 Attenuates Inflammatory Response and Improves Cognitive Function in Chronic Ischemic Stroke Mice.坏死抑制因子-1减轻慢性缺血性脑卒中小鼠的炎症反应并改善其认知功能。
Medicines (Basel). 2016 Jul 1;3(3):16. doi: 10.3390/medicines3030016.
3
Interferon-gamma regulates inflammatory cell death by targeting necroptosis in experimental autoimmune arthritis.
RIPK1在斑秃中的作用
Int J Mol Sci. 2025 Feb 13;26(4):1565. doi: 10.3390/ijms26041565.
4
Programmed Cell Death in Rheumatoid Arthritis.类风湿关节炎中的程序性细胞死亡
J Inflamm Res. 2025 Feb 18;18:2377-2393. doi: 10.2147/JIR.S499345. eCollection 2025.
5
Deciphering Immunometabolic Landscape in Rheumatoid Arthritis: Integrative Multiomics, Explainable Machine Learning and Experimental Validation.解析类风湿关节炎中的免疫代谢格局：整合多组学、可解释机器学习与实验验证
J Inflamm Res. 2025 Jan 16;18:637-652. doi: 10.2147/JIR.S503118. eCollection 2025.
6
The role of AIM2 in inflammation and tumors.AIM2 在炎症和肿瘤中的作用。
Front Immunol. 2024 Nov 12;15:1466440. doi: 10.3389/fimmu.2024.1466440. eCollection 2024.
7
Cytoplasmic DNA and AIM2 inflammasome in RA: where they come from and where they go?细胞质 DNA 与 RA 中的 AIM2 炎性体：它们从何而来，又将去往何处？
Front Immunol. 2024 Oct 10;15:1343325. doi: 10.3389/fimmu.2024.1343325. eCollection 2024.
8
Association of RIPK1 and RIPK2 Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Han Population.中国汉族人群中RIPK1和RIPK2基因多态性与类风湿关节炎的关联
Appl Clin Genet. 2024 Oct 19;17:159-169. doi: 10.2147/TACG.S472418. eCollection 2024.
9
Necrostatin-1: a promising compound for neurological disorders.坏死抑制因子-1：一种治疗神经疾病的有前景的化合物。
Front Cell Neurosci. 2024 Jun 27;18:1408364. doi: 10.3389/fncel.2024.1408364. eCollection 2024.
10
Dying to Defend: Neutrophil Death Pathways and their Implications in Immunity.《垂死防御：中性粒细胞死亡途径及其在免疫中的意义》。
Adv Sci (Weinh). 2024 Feb;11(8):e2306457. doi: 10.1002/advs.202306457. Epub 2023 Dec 3.
干扰素-γ通过靶向实验性自身免疫性关节炎中的坏死性凋亡来调节炎症细胞死亡。
Sci Rep. 2017 Aug 31;7(1):10133. doi: 10.1038/s41598-017-09767-0.
4
Coenzyme Q10 Inhibits Th17 and STAT3 Signaling Pathways to Ameliorate Colitis in Mice.辅酶Q10抑制Th17和STAT3信号通路以改善小鼠结肠炎
J Med Food. 2017 Sep;20(9):821-829. doi: 10.1089/jmf.2016.3859. Epub 2017 Aug 17.
5
Ssu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation.Ssu72 通过靶向 STAT3 信号和 Th17 激活来减轻自身免疫性关节炎。
Sci Rep. 2017 Jul 14;7(1):5506. doi: 10.1038/s41598-017-05421-x.
6
Inhibition of Receptor-Interacting Protein Kinase 1 with Necrostatin-1s ameliorates disease progression in elastase-induced mouse abdominal aortic aneurysm model.使用 Necrostatin-1s 抑制受体相互作用蛋白激酶 1 可改善弹性蛋白酶诱导的小鼠腹主动脉瘤模型的疾病进展。
Sci Rep. 2017 Feb 10;7:42159. doi: 10.1038/srep42159.
7
HtrA2 suppresses autoimmune arthritis and regulates activation of STAT3.HtrA2 抑制自身免疫性关节炎并调节 STAT3 的激活。
Sci Rep. 2016 Dec 23;6:39393. doi: 10.1038/srep39393.
8
PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs.PTEN 通过下调 STAT3 激活来改善自身免疫性关节炎，同时维持 Th17 和 Tregs 的平衡。
Sci Rep. 2016 Oct 6;6:34617. doi: 10.1038/srep34617.
9
GRIM19 ameliorates acute graft-versus-host disease (GVHD) by modulating Th17 and Treg cell balance through down-regulation of STAT3 and NF-AT activation.GRIM19通过下调STAT3和NF-AT的激活来调节Th17和Treg细胞平衡，从而改善急性移植物抗宿主病（GVHD）。
J Transl Med. 2016 Jul 8;14(1):206. doi: 10.1186/s12967-016-0963-0.
10
(p40)2-Fc reduces immune-inflammatory response through the activation of T cells in collagen induced arthritis mice.（p40）2-Fc通过激活胶原诱导性关节炎小鼠的T细胞来降低免疫炎症反应。
Immunol Lett. 2016 Aug;176:36-43. doi: 10.1016/j.imlet.2016.05.013. Epub 2016 May 23.