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Int Immunopharmacol. 2018 Feb;55:174-182. doi: 10.1016/j.intimp.2017.12.011. Epub 2017 Dec 22.

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

Author information

1
Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
2
School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong, China.
3
School of Traditional Chinese Medicine, the Southern Medical University, Guangzhou, Guangdong, China.
4
Department of Rheumatology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
5
School of Traditional Chinese Medicine, the Southern Medical University, Guangzhou, Guangdong, China. Electronic address: zhaoxs0609@163.com.
6
Department of Rheumatology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China. Electronic address: linchs999@163.com.

Abstract

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.

KEYWORDS:

Fibroblast-like synoviocyte; Invasion; Kaempferol; MAPK; Migration; Rheumatoid arthritis

PMID:
29268189
DOI:
10.1016/j.intimp.2017.12.011
[Indexed for MEDLINE]

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