• 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

白细胞介素-1α 是人类支气管成纤维细胞对嗜酸性粒细胞炎症反应的关键介质。

Interleukin-1α Is a Critical Mediator of the Response of Human Bronchial Fibroblasts to Eosinophilic Inflammation.

机构信息

Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA.

出版信息

Cells. 2021 Mar 2;10(3):528. doi: 10.3390/cells10030528.

DOI:10.3390/cells10030528
PMID:33801398
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7998867/
Abstract

Eosinophils contribute to allergic inflammation in asthma in part via elaboration of a complex milieu of soluble mediators. Human bronchial fibroblasts (HBF) respond to stimulation by these mediators by acquiring a pro-inflammatory profile including induction of interleukin 6 (IL6) and IL8. This study sought to determine key component(s) of eosinophil soluble factors that mediate IL6 and IL8 induction in HBF. HBF treated with eosinophil-derived soluble mediators were analyzed for gene expression, intracellular signaling, and IL6 and IL8 secretion following inhibition of inflammatory signaling. Segmental allergen bronchoprovocation (SBP-Ag) was performed in mild asthmatics and bronchoalveolar lavage fluid was analyzed for eosinophils and cytokines. We found that signaling via the IL1α/IL1 receptor is an essential component of the response of HBF to eosinophil-derived soluble factors. IL1α-dependent activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling is required to induce IL6 secretion. However, NFκB signaling is dispensable for the induction of IL8, whereas Src is required. IL1α is associated with eosinophilic inflammation in human airways after SBP-Ag. Conclusions: IL1α appears to be a critical component of the soluble eosinophil-derived milieu that drives pro-inflammatory bronchial fibroblast responses and associates with eosinophilic inflammation following SBP-Ag. Disruption of IL1α-signaling could modify the downstream effects of eosinophilic inflammation on airway remodeling.

摘要

嗜酸性粒细胞通过分泌大量可溶性介质在哮喘的变应性炎症中发挥作用。这些介质可刺激人支气管成纤维细胞(HBF)获得促炎表型,包括诱导白细胞介素 6(IL6)和白细胞介素 8(IL8)的表达。本研究旨在确定介导 HBF 中 IL6 和 IL8 诱导的嗜酸性粒细胞可溶性因子的关键成分。用嗜酸性粒细胞衍生的可溶性介质处理 HBF 后,通过抑制炎症信号转导分析基因表达、细胞内信号转导以及 IL6 和 IL8 的分泌。对轻度哮喘患者进行分段变应原支气管激发(SBP-Ag),并分析支气管肺泡灌洗液中的嗜酸性粒细胞和细胞因子。结果发现,IL1α/IL1 受体信号转导是 HBF 对嗜酸性粒细胞衍生的可溶性因子反应的重要组成部分。IL1α 依赖性核因子 kappa 轻链增强子的 B 细胞(NFκB)信号转导的激活对于诱导 IL6 分泌是必需的。然而,NFκB 信号转导对于 IL8 的诱导是可有可无的,而 Src 是必需的。在 SBP-Ag 后,IL1α 与人类气道中的嗜酸性粒细胞炎症相关。结论:IL1α 似乎是驱动促炎性支气管成纤维细胞反应的嗜酸性粒细胞衍生的可溶性微环境的关键成分,并与 SBP-Ag 后嗜酸性粒细胞炎症相关。阻断 IL1α 信号转导可能会改变嗜酸性粒细胞炎症对气道重塑的下游影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/532c79b4e80f/cells-10-00528-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/eb1d5f4a1a15/cells-10-00528-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/9038fe5a3ce6/cells-10-00528-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/4318252a6366/cells-10-00528-g0A3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/89d5a79dc963/cells-10-00528-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/da881479f8d5/cells-10-00528-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/3afb3529b2a0/cells-10-00528-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/aeb1435b46ed/cells-10-00528-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/19379cf97aa2/cells-10-00528-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/5091f039e849/cells-10-00528-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/532c79b4e80f/cells-10-00528-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/eb1d5f4a1a15/cells-10-00528-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/9038fe5a3ce6/cells-10-00528-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/4318252a6366/cells-10-00528-g0A3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/89d5a79dc963/cells-10-00528-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/da881479f8d5/cells-10-00528-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/3afb3529b2a0/cells-10-00528-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/aeb1435b46ed/cells-10-00528-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/19379cf97aa2/cells-10-00528-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/5091f039e849/cells-10-00528-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491a/7998867/532c79b4e80f/cells-10-00528-g007.jpg

相似文献

1
Interleukin-1α Is a Critical Mediator of the Response of Human Bronchial Fibroblasts to Eosinophilic Inflammation.白细胞介素-1α 是人类支气管成纤维细胞对嗜酸性粒细胞炎症反应的关键介质。
Cells. 2021 Mar 2;10(3):528. doi: 10.3390/cells10030528.
2
RNA-sequencing analysis of lung primary fibroblast response to eosinophil-degranulation products predicts downstream effects on inflammation, tissue remodeling and lipid metabolism.肺原代成纤维细胞对嗜酸性粒细胞脱颗粒产物反应的 RNA 测序分析预测了对炎症、组织重塑和脂质代谢的下游影响。
Respir Res. 2017 Nov 10;18(1):188. doi: 10.1186/s12931-017-0669-8.
3
IL-5 and IL-5 receptor in asthma.哮喘中的白细胞介素-5和白细胞介素-5受体
Mem Inst Oswaldo Cruz. 1997;92 Suppl 2:75-91. doi: 10.1590/s0074-02761997000800012.
4
Mepolizumab Attenuates Airway Eosinophil Numbers, but Not Their Functional Phenotype, in Asthma.美泊利单抗可减少哮喘患者气道中的嗜酸性粒细胞数量,但不改变其功能表型。
Am J Respir Crit Care Med. 2017 Dec 1;196(11):1385-1395. doi: 10.1164/rccm.201611-2234OC.
5
Airway hyperresponsiveness: first eosinophils and then neuropeptides.气道高反应性:先是嗜酸性粒细胞,然后是神经肽。
Int J Immunopharmacol. 1997 Sep-Oct;19(9-10):517-27. doi: 10.1016/s0192-0561(97)00085-4.
6
Airway eosinophilic inflammation and bronchial hyperresponsiveness after allergen inhalation challenge in asthma.哮喘患者吸入变应原激发试验后的气道嗜酸性粒细胞炎症和支气管高反应性
Lung. 1998;176(4):237-47. doi: 10.1007/pl00007606.
7
Eosinophil-Derived Osteopontin Induces the Expression of Pro-Inflammatory Mediators and Stimulates Extracellular Matrix Production in Nasal Fibroblasts: The Role of Osteopontin in Eosinophilic Chronic Rhinosinusitis.嗜酸性粒细胞衍生的骨桥蛋白诱导鼻成纤维细胞表达促炎介质并刺激细胞外基质产生:骨桥蛋白在嗜酸性粒细胞性慢性鼻-鼻窦炎中的作用。
Front Immunol. 2022 Mar 2;13:777928. doi: 10.3389/fimmu.2022.777928. eCollection 2022.
8
Eosinophil-fibroblast interactions induce fibroblast IL-6 secretion and extracellular matrix gene expression: implications in fibrogenesis.嗜酸性粒细胞与成纤维细胞的相互作用诱导成纤维细胞分泌白细胞介素-6及细胞外基质基因表达:对纤维化形成的影响。
J Allergy Clin Immunol. 2005 Oct;116(4):796-804. doi: 10.1016/j.jaci.2005.06.031.
9
Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma.白细胞介素-7在哮喘变应原诱导的嗜酸性粒细胞性气道炎症中的潜在作用。
J Immunol. 2009 Feb 1;182(3):1404-10. doi: 10.4049/jimmunol.182.3.1404.
10
Increased IL-6 and Potential IL-6 trans-signalling in the airways after an allergen challenge.过敏原刺激后气道中白细胞介素 6(IL-6)的增加和潜在的 IL-6 转导信号。
Clin Exp Allergy. 2021 Apr;51(4):564-573. doi: 10.1111/cea.13832. Epub 2021 Feb 2.

引用本文的文献

1
Biomarkers Reflecting the Severity of Bronchial Asthma in Children.反映儿童支气管哮喘严重程度的生物标志物。
J Asthma Allergy. 2024 Nov 29;17:1227-1237. doi: 10.2147/JAA.S486958. eCollection 2024.
2
Integrative Cross-Talk in Asthma: Unraveling the Complex Interactions Between Eosinophils, Immune, and Structural Cells in the Airway Microenvironment.哮喘中的整合性相互作用:揭示气道微环境中嗜酸性粒细胞、免疫细胞和结构细胞之间的复杂相互作用
Diagnostics (Basel). 2024 Oct 31;14(21):2448. doi: 10.3390/diagnostics14212448.
3
Development of Adaptive Immunity and Its Role in Lung Remodeling.

本文引用的文献

1
Increased IL-6 and Potential IL-6 trans-signalling in the airways after an allergen challenge.过敏原刺激后气道中白细胞介素 6(IL-6)的增加和潜在的 IL-6 转导信号。
Clin Exp Allergy. 2021 Apr;51(4):564-573. doi: 10.1111/cea.13832. Epub 2021 Feb 2.
2
Eosinophil cytolysis on Immunoglobulin G is associated with microtubule formation and suppression of rho-associated protein kinase signalling.免疫球蛋白 G 介导的嗜酸性粒细胞溶解与微管形成和 rho 相关蛋白激酶信号通路抑制有关。
Clin Exp Allergy. 2020 Feb;50(2):198-212. doi: 10.1111/cea.13538. Epub 2019 Dec 9.
3
Defective Fibrillar Collagen Organization by Fibroblasts Contributes to Airway Remodeling in Asthma.
适应性免疫的发展及其在肺重塑中的作用。
Adv Exp Med Biol. 2023;1426:287-351. doi: 10.1007/978-3-031-32259-4_14.
4
Understanding fibroblast-immune cell interactions co-culture models and their role in asthma pathogenesis.了解成纤维细胞-免疫细胞相互作用的共培养模型及其在哮喘发病机制中的作用。
Front Immunol. 2023 Feb 23;14:1128023. doi: 10.3389/fimmu.2023.1128023. eCollection 2023.
5
An open microfluidic coculture model of fibroblasts and eosinophils to investigate mechanisms of airway inflammation.一种用于研究气道炎症机制的成纤维细胞和嗜酸性粒细胞的开放式微流控共培养模型。
Front Bioeng Biotechnol. 2022 Sep 29;10:993872. doi: 10.3389/fbioe.2022.993872. eCollection 2022.
6
Airway fibrin formation cascade in allergic asthma exacerbation: implications for inflammation and remodeling.过敏性哮喘加重期气道纤维蛋白形成级联反应:对炎症和重塑的影响
Clin Proteomics. 2022 May 19;19(1):15. doi: 10.1186/s12014-022-09351-3.
7
Role of amygdala in stress-induced upregulation of airway IL-1 signaling in asthma.杏仁核在应激诱导哮喘气道 IL-1 信号转导上调中的作用。
Biol Psychol. 2022 Jan;167:108226. doi: 10.1016/j.biopsycho.2021.108226. Epub 2021 Nov 17.
8
Eosinophils, beyond IL-5.嗜酸性粒细胞,不仅仅与白细胞介素 5 相关。
Cells. 2021 Oct 1;10(10):2615. doi: 10.3390/cells10102615.
成纤维细胞的纤维状胶原组织缺陷导致哮喘气道重塑。
Am J Respir Crit Care Med. 2019 Aug 15;200(4):431-443. doi: 10.1164/rccm.201810-1855OC.
4
Matrix Metalloproteinase-9-Dependent Release of IL-1 by Human Eosinophils.人嗜酸性粒细胞中基质金属蛋白酶-9 依赖性白细胞介素-1 的释放。
Mediators Inflamm. 2019 Feb 17;2019:7479107. doi: 10.1155/2019/7479107. eCollection 2019.
5
Eosinophil-degranulation products drive a proinflammatory fibroblast phenotype.嗜酸性粒细胞脱颗粒产物驱动促炎成纤维细胞表型。
J Allergy Clin Immunol. 2018 Oct;142(4):1360-1363.e3. doi: 10.1016/j.jaci.2018.05.037. Epub 2018 Jun 21.
6
RNA-sequencing analysis of lung primary fibroblast response to eosinophil-degranulation products predicts downstream effects on inflammation, tissue remodeling and lipid metabolism.肺原代成纤维细胞对嗜酸性粒细胞脱颗粒产物反应的 RNA 测序分析预测了对炎症、组织重塑和脂质代谢的下游影响。
Respir Res. 2017 Nov 10;18(1):188. doi: 10.1186/s12931-017-0669-8.
7
Mepolizumab Attenuates Airway Eosinophil Numbers, but Not Their Functional Phenotype, in Asthma.美泊利单抗可减少哮喘患者气道中的嗜酸性粒细胞数量,但不改变其功能表型。
Am J Respir Crit Care Med. 2017 Dec 1;196(11):1385-1395. doi: 10.1164/rccm.201611-2234OC.
8
IL-3 up-regulates and activates human eosinophil CD32 and αMβ2 integrin causing degranulation.白细胞介素-3上调并激活人类嗜酸性粒细胞的CD32和αMβ2整合素,导致脱颗粒。
Clin Exp Allergy. 2017 Apr;47(4):488-498. doi: 10.1111/cea.12876. Epub 2017 Jan 23.
9
Airway factor XIII associates with type 2 inflammation and airway obstruction in asthmatic patients.气道凝血因子 XIII 与哮喘患者的 2 型炎症和气道阻塞相关。
J Allergy Clin Immunol. 2016 Mar;137(3):767-73.e6. doi: 10.1016/j.jaci.2015.05.053. Epub 2015 Oct 30.
10
Eosinophil extracellular trap cell death-derived DNA traps: Their presence in secretions and functional attributes.嗜酸性粒细胞胞外诱捕细胞死亡衍生的DNA陷阱:它们在分泌物中的存在及功能特性。
J Allergy Clin Immunol. 2016 Jan;137(1):258-267. doi: 10.1016/j.jaci.2015.04.041. Epub 2015 Jun 9.