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学科主题: 临床医学
题名:
A formyl peptide receptor agonist suppresses inflammation and bone damage in arthritis
作者: 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
发表日期: 2014-09-01
DOI: 10.1111/bph.12768
卷: 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
所属项目编号: 1008991
项目资助者: National Health and Medical Research Council of Australia
WOS记录号: WOS:000340509600012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50208
Appears in Collections:北京大学第二临床医学院_期刊论文

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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

Recommended Citation:
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.
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