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学科主题临床医学
A formyl peptide receptor agonist suppresses inflammation and bone damage in arthritis
Kao, W.1,2; Gu, R.1; Jia, Y.1,3; Wei, Xuemin1,4; Fan, H.1; Harris, J.1; Zhang, Zhiyi4; Quinn, J.5,6; Morand, E. F.1; Yang, Y. H.1
刊名BRITISH JOURNAL OF PHARMACOLOGY
2014-09-01
DOI10.1111/bph.12768
171期:17页:4087-4096
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]FIBROBLAST-LIKE SYNOVIOCYTES ; ANNEXIN A1 ; RHEUMATOID-ARTHRITIS ; LIPOXIN A(4) ; DUAL AGONIST ; IN-VIVO ; GLUCOCORTICOIDS ; LIGAND ; EXPRESSION ; PROTEIN
英文摘要

BACKGROUND AND PURPOSE

Annexin A1 (AnxA1) is an endogenous anti-inflammatory protein and agonist of the formyl peptide receptor 2 (FPR2). However, the potential for therapeutic FPR ligands to modify immune-mediated disease has been little explored. We investigated the effects of a synthetic FPR agonist on joint disease in the K/BxN model of rheumatoid arthritis (RA) and RA fibroblast-like synoviocytes (FLS).

EXPERIMENTAL APPROACH

Arthritis was induced by injection of K/BxN serum at day 0 and 2 in wild-type (WT) or AnxA1(-/-) mice and clinical and histopathological manifestations measured 8-11 days later. WT mice were given the FPR agonist compound 43 (Cpd43) (6 or 30 mg kg(-1) i.p.) for 4 days. Effects of AnxA1 and Cpd43 on RANKL-induced osteoclastogenesis were assessed in RAW 264.7 cells and human RA FLS and macrophages.

KEY RESULTS

Treatment with Cpd43 before or after the onset of arthritis reduced clinical disease severity and attenuated synovial TNF-alpha and osteoclast-associated gene expression. Deletion of AnxA1 in mice exacerbated arthritis severity in the K/BxN model. In vitro, Cpd43 suppressed osteoclastogenesis and NFAT activity elicited by RANKL, and inhibited IL-6 secretion by mouse macrophages. In human RA joint-derived FLS and monocyte-derived macrophages, Cpd43 treatment inhibited IL-6 release, while blocking FPR2 or silencing AnxA1 increased this release.

CONCLUSIONS AND IMPLICATIONS

The FPR agonist Cpd43 reduced osteoclastogenesis and inflammation in a mouse model of RA and exhibited anti-inflammatory effects in relevant human cells. These data suggest that FPR ligands may represent novel therapeutic agents capable of ameliorating inflammation and bone damage in RA.

语种英语
WOS记录号WOS:000340509600012
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50208
专题北京大学第二临床医学院
作者单位1.Monash Univ, Monash Med Ctr, Fac Med Nursing & Hlth Sci, Ctr Inflammatory Dis, Clayton, Vic 3168, Australia
2.Harbin Med Univ, Dept Microbiol, Harbin, Peoples R China
3.Peking Univ, Peoples Hosp, Dept Rheumatol & Immunol, Beijing 100871, Peoples R China
4.Harbin Med Univ, Affiliated Hosp 1, Dept Rheumatol, Harbin, Peoples R China
5.Monash Med Ctr, Prince Henrys Inst, Clayton, Vic 3168, Australia
6.Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3168, Australia
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Kao, W.,Gu, R.,Jia, Y.,et al. A formyl peptide receptor agonist suppresses inflammation and bone damage in arthritis[J]. BRITISH JOURNAL OF PHARMACOLOGY,2014,171(17):4087-4096.
APA Kao, W..,Gu, R..,Jia, Y..,Wei, Xuemin.,Fan, H..,...&Yang, Y. H..(2014).A formyl peptide receptor agonist suppresses inflammation and bone damage in arthritis.BRITISH JOURNAL OF PHARMACOLOGY,171(17),4087-4096.
MLA Kao, W.,et al."A formyl peptide receptor agonist suppresses inflammation and bone damage in arthritis".BRITISH JOURNAL OF PHARMACOLOGY 171.17(2014):4087-4096.
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