Mechanosensitive TRPV4 is required for crystal-induced inflammation

炎症体 TRPV4型 炎症 医学 关节炎 体内 瞬时受体电位通道 促炎细胞因子 细胞生物学 免疫学 生物 内科学 受体 生物技术
作者
Zhou Lan,Lvyi Chen,Jing Feng,Zili Xie,Yong Li,Fang Wang,Peng Liu,Xiumei Yue,Lixia Du,Yue Zhao,Yang Pu,Jialie Luo,Zhe Zhu,Xueming Hu,Cao Liang,Ping Lü,Rajan Sah,Kory J. Lavine,Brian Kim,Hongzhen Hu
出处
期刊:Annals of the Rheumatic Diseases [BMJ]
卷期号:80 (12): 1604-1614 被引量:38
标识
DOI:10.1136/annrheumdis-2021-220295
摘要

Crystal structures activate innate immune cells, especially macrophages and initiate inflammatory responses. We aimed to understand the role of the mechanosensitive TRPV4 channel in crystal-induced inflammation. Real-time RT-PCR, RNAscope in situ hybridisation, and Trpv4eGFP mice were used to examine TRPV4 expression and whole-cell patch-clamp recording and live-cell Ca2+ imaging were used to study TRPV4 function in mouse synovial macrophages and human peripheral blood mononuclear cells (PBMCs). Both genetic deletion and pharmacological inhibition approaches were used to investigate the role of TRPV4 in NLRP3 inflammasome activation induced by diverse crystals in vitro and in mouse models of crystal-induced pain and inflammation in vivo. TRPV4 was functionally expressed by synovial macrophages and human PBMCs and TRPV4 expression was upregulated by stimulation with monosodium urate (MSU) crystals and in human PBMCs from patients with acute gout flares. MSU crystal-induced gouty arthritis were significantly reduced by either genetic ablation or pharmacological inhibition of TRPV4 function. Mechanistically, TRPV4 mediated the activation of NLRP3 inflammasome by diverse crystalline materials but not non-crystalline NLRP3 inflammasome activators, driving the production of inflammatory cytokine interleukin-1β which elicited TRPV4-dependent inflammatory responses in vivo. Moreover, chemical ablation of the TRPV1-expressing nociceptors significantly attenuated the MSU crystal-induced gouty arthritis. In conclusion, TRPV4 is a common mediator of inflammatory responses induced by diverse crystals through NLRP3 inflammasome activation in macrophages. TRPV4-expressing resident macrophages are critically involved in MSU crystal-induced gouty arthritis. A neuroimmune interaction between the TRPV1-expressing nociceptors and the TRPV4-expressing synovial macrophages contributes to the generation of acute gout flares.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
小废物完成签到,获得积分10
3秒前
天天快乐应助彭凯采纳,获得10
3秒前
5秒前
5秒前
5秒前
北风和你完成签到,获得积分10
6秒前
MY完成签到,获得积分20
7秒前
英俊的铭应助niu采纳,获得10
7秒前
硕果累累关注了科研通微信公众号
8秒前
白好闻发布了新的文献求助30
10秒前
aaaaa发布了新的文献求助10
10秒前
初夏发布了新的文献求助10
12秒前
bravo发布了新的文献求助10
13秒前
Sunshine完成签到,获得积分10
13秒前
13秒前
aaaaa完成签到,获得积分10
15秒前
18秒前
华仔应助嘻嘻采纳,获得10
19秒前
牛牛完成签到,获得积分10
21秒前
基莲发布了新的文献求助10
23秒前
melody发布了新的文献求助10
25秒前
27秒前
所所应助研友_LXONx8采纳,获得50
28秒前
28秒前
28秒前
Owen应助顺心的筮采纳,获得10
28秒前
枯藤老树昏呀完成签到,获得积分10
28秒前
昆仑山吴某完成签到 ,获得积分10
29秒前
niu发布了新的文献求助10
31秒前
落寞怜雪完成签到,获得积分10
33秒前
万里完成签到,获得积分10
34秒前
亲亲亲完成签到,获得积分20
34秒前
bravo完成签到,获得积分10
35秒前
贺忻发布了新的文献求助10
36秒前
完美世界应助怡然尔白采纳,获得10
36秒前
SOLOMON应助落寞怜雪采纳,获得10
38秒前
shinysparrow应助Jeffrey采纳,获得30
39秒前
七月完成签到 ,获得积分20
39秒前
xqw完成签到 ,获得积分10
40秒前
ZQYYRA发布了新的文献求助10
41秒前
高分求助中
请在求助之前详细阅读求助说明!!!! 20000
One Man Talking: Selected Essays of Shao Xunmei, 1929–1939 1000
The Three Stars Each: The Astrolabes and Related Texts 900
Yuwu Song, Biographical Dictionary of the People's Republic of China 800
Multifunctional Agriculture, A New Paradigm for European Agriculture and Rural Development 600
Bernd Ziesemer - Maos deutscher Topagent: Wie China die Bundesrepublik eroberte 500
A radiographic standard of reference for the growing knee 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2477094
求助须知:如何正确求助?哪些是违规求助? 2141016
关于积分的说明 5457187
捐赠科研通 1864263
什么是DOI,文献DOI怎么找? 926775
版权声明 562872
科研通“疑难数据库(出版商)”最低求助积分说明 495884