Kaempferol inhibits the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes by blocking activation of the MAPK pathway

山奈酚 细胞迁移 MAPK/ERK通路 肿瘤坏死因子α 化学 癌症研究 体内 受体 基质金属蛋白酶 细胞生物学 信号转导 体外 免疫学 生物 生物化学 类黄酮 生物技术 抗氧化剂
作者
Dongmei Pan,Nan Li,Yanyan Liu,Qiang Xu,Qingping Liu,Yanting You,Zhenquan Wei,Yubao Jiang,Lei Zhu,Tianfeng Guo,Xudong Cai,Xiaobao Liu,Qiang Wang,Mingling Liu,Xujie Lei,Mingying Zhang,Xiaoshan Zhao,Changsong Lin
出处
期刊:International Immunopharmacology [Elsevier]
卷期号:55: 174-182 被引量:94
标识
DOI:10.1016/j.intimp.2017.12.011
摘要

In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLSs) play an essential role in cartilage destruction. Aggressive migration and invasion by FLSs significantly affect RA pathology. Kaempferol has been shown to inhibit cancer cell migration and invasion. However, the effects of kaempferol on RA FLSs have not been investigated. Our study aimed to determine the effects of kaempferol on RA both in vitro and in vivo. In vitro, cell migration and invasion were measured using scratch assays and the Boyden chamber method, respectively. The cytoskeletal reorganization of RA FLSs was evaluated by immunofluorescence staining. Matrix metalloproteinase (MMP) levels were measured by real-time PCR, and protein expression levels were measured by western blotting. In vivo, the effects of kaempferol were evaluated in mice with CIA. The results showed that kaempferol reduced migration, invasion and MMP expression in RA FLSs. In addition, we demonstrated that kaempferol inhibited reorganization of the actin cytoskeleton during cell migration. Moreover, kaempferol dramatically suppressed tumor necrosis factor (TNF)-α-induced MAPK activation without affecting the expression of TNF-α receptors. We also demonstrated that kaempferol attenuated the severity of arthritis in mice with CIA. Taken together, these results suggested that kaempferol inhibits the migration and invasion of FLSs in RA by blocking MAPK pathway activation without affecting the expression of TNF-α receptors.
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