Kaempferol inhibits IL-1β-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of COX-2, PGE2 and MMPs

• Published in: International journal of molecular medicine 2013-10, Vol.32 (4), p.971-977
• Main Authors: YOON, HA-YONG, LEE, EUN-GYEONG, LEE, HYUN, CHO, IN JIN, CHOI, YUN JUNG, SUNG, MYUNG-SOON, YOO, HAN-GYUL, YOO, WAN-HEE
• Format: Article
• Language: English
• Subjects: Apoptosis; Cell growth; cyclooxygenase; Fibroblasts; Flavonoids; Government agencies; Inflammation; interleukin-1β; Joint surgery; kaempferol; Kinases; matrix metalloproteinases; Pathogenesis; Phosphorylation; prostaglandin E2; Proteins; Rheumatoid arthritis; Rodents; Studies; Tumor necrosis factor-TNF
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2013.1468

Inflammatory cytokines, matrix metalloproteinases (MMPs) and cyclooxygenase (COX)-2 released from rheumatoid arthritis synovial fibroblasts (RASFs) are involved in the destruction of both articular bone and cartilage. Kaempferol has been reported to act as an antioxidant and anti-inflammatory agent by inhibiting nitric oxide synthase and COX enzymes. The aim of the present study was to determine the effects of kaempferol on the interleukin-1β (IL-1β)-induced proliferation of RASFs and the production of MMPs, COX and prostaglandin E2 (PGE2) by RASFs. The proliferation of the RASFs stimulated with IL-1β and treated with/without kaempferol was evaluated by CCK-8 assay. The expression of MMPs, TIMP metallopeptidase inhibitor-1 (TIMP-1), COXs, PGE2 and that of intracellular MAPK signaling molecules, including p-ERK, p-p38, p-JNK and nuclear factor-κB (NF-κB) was examined by immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and ELISA under the conditions described above. Kaempferol inhibited the proliferation of both unstimulated and IL-1β-stimulated RASFs, as well as the mRNA and protein expression of MMP-1, MMP-3, COX-2 and PGE2 induced by IL-1β. Kaempferol also inhibited the phosphorylation of ERK-1/2, p38 and JNK, as well as the activation of NF-κB induced by IL-1β. These results indicate that kaempferol inhibits synovial fibroblast proliferation, as well as the production of and MMPs, COX-2 and PGE2, which is involved in articular inflammation and destruction in rheumatoid arthritis (RA). Our data suggest that kaempferol may be a novel therapeutic agent for the treatment of RA.