GPR84 regulates pulmonary inflammation by modulating neutrophil functions

doi:10.1038/s41401-023-01080-z

KMS@SIMM > 新药研究国家重点实验室

	GPR84 regulates pulmonary inflammation by modulating neutrophil functions
	Wang, Si-wei 1,2; Zhang, Qing1,3,4 ; Lu, Dan 5; Fang, You-chen 1; Yan, Xiao-ci 1,2,3; Chen, Jing1,2 ; Xia, Zhi-kan 1,2; Yuan, Qian-ting 1; Chen, Lin-hai1 ; Zhang, Yang-ming 6; Nan, Fa-jun1,3,4 ; Xie, Xin1,2,3,4,5
	2023-08-01
发表期刊	ACTA PHARMACOLOGICA SINICA (IF:3.562[JCR-2017],3.773[5-Year])
卷号	44 期号:8 页码:1665-1675
摘要	Acute lung injury (ALI) is an acute, progressive hypoxic respiratory failure that could develop into acute respiratory distress syndrome (ARDS) with very high mortality rate. ALI is believed to be caused by uncontrolled inflammation, and multiple types of immune cells, especially neutrophils, are critically involved in the development of ALI. The treatment for ALI/ARDS is very limited, a better understanding of the pathogenesis and new therapies are urgently needed. Here we discover that GPR84, a medium chain fatty acid receptor, plays critical roles in ALI development by regulating neutrophil functions. GPR84 is highly upregulated in the cells isolated from the bronchoalveolar lavage fluid of LPS-induced ALI mice. GPR84 deficiency or blockage significantly ameliorated ALI mice lung inflammation by reducing neutrophils infiltration and oxidative stress. Further studies reveal that activation of GPR84 strongly induced reactive oxygen species production from neutrophils by stimulating Lyn, AKT and ERK1/2 activation and the assembly of the NADPH oxidase. These results reveal an important role of GPR84 in neutrophil functions and lung inflammation and strongly suggest that GPR84 is a potential drug target for ALI.
关键词	GPR84 acute lung injury inflammation neutrophil ROS antagonist
WOS关键词	ACUTE LUNG INJURY ; RESPIRATORY-DISTRESS-SYNDROME ; NADPH OXIDASE ; NOX FAMILY ; RECEPTOR ; DEGRANULATION ; PATHOGENESIS ; RECRUITMENT ; ANTAGONISTS ; ACTIVATION
文献子类	Article
DOI	10.1038/s41401-023-01080-z
收录类别	SCIE
语种	英语
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
WOS记录号	WOS:000962657100001
出版者	NATURE PUBL GROUP
引用统计	被引频次：22[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.183/handle/2S10ELR8/309653
专题	新药研究国家重点实验室
通讯作者	Xie, Xin
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China; 4.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China; 5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China; 6.Burgeon Therapeut Co Ltd, Shanghai 201203, Peoples R China
第一作者单位	国家新药筛选中心
通讯作者单位	国家新药筛选中心
推荐引用方式 GB/T 7714	Wang, Si-wei,Zhang, Qing,Lu, Dan,et al. GPR84 regulates pulmonary inflammation by modulating neutrophil functions[J]. ACTA PHARMACOLOGICA SINICA,2023,44(8):1665-1675.
APA	Wang, Si-wei.,Zhang, Qing.,Lu, Dan.,Fang, You-chen.,Yan, Xiao-ci.,...&Xie, Xin.(2023).GPR84 regulates pulmonary inflammation by modulating neutrophil functions.ACTA PHARMACOLOGICA SINICA,44(8),1665-1675.
MLA	Wang, Si-wei,et al."GPR84 regulates pulmonary inflammation by modulating neutrophil functions".ACTA PHARMACOLOGICA SINICA 44.8(2023):1665-1675.