Kaempferol inhibits IL-1β-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of COX-2, PGE2 and MMPs
Kaempferol inhibits IL-1β-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of COX-2, PGE2 and MMPs
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DOI：
10.3892/ijmm.2013.1468
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发表时间：
2013-10-01
影响因子：
5.4
通讯作者：
Yoo, Wan-Hee
中科院分区：
文献类型：
--
作者：
Yoon, Ha-Yong;Lee, Eun-Gyeong;Yoo, Wan-Hee
类风湿性关节炎滑膜成纤维细胞 (RASF) 释放的炎症细胞因子、基质金属蛋白酶 (MMP) 和环氧合酶 (COX)-2 参与关节骨和软骨的破坏。据报道，山奈酚通过抑制一氧化氮合酶和 COX 酶而充当抗氧化剂和抗炎剂。本研究的目的是确定山奈酚对白介素 1 β (IL-1 β) 诱导的 RASF 增殖以及 RASF 产生 MMP、COX 和前列腺素 E2 (PGE2) 的影响。通过CCK-8测定评估用IL-1β刺激并用/不用山奈酚处理的RASF的增殖。通过免疫印迹或半定量逆转录聚合酶链反应（RT-PCR）检测MMP、TIMP金属肽酶抑制剂-1（TIMP-1）、COX、PGE2以及细胞内MAPK信号分子的表达，包括p-ERK、p-p38、p-JNK和核因子-κB（NF-κB） 在上述条件下进行 ELISA。山奈酚抑制未刺激和IL-1β刺激的RASF的增殖，以及IL-1β诱导的MMP-1、MMP-3、COX-2和PGE2的mRNA和蛋白表达。山奈酚还抑制 ERK-1/2、p38 和 JNK 的磷酸化，以及 IL-1 β 诱导的 NF-κ B 的激活。这些结果表明，山奈酚抑制滑膜成纤维细胞增殖，以及 MMP、COX-2 和 PGE2 的产生，这些物质参与类风湿性关节炎 (RA) 的关节炎症和破坏。我们的数据表明山奈酚可能是治疗 RA 的新型治疗剂。
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-1 beta (IL-1 beta)-induced proliferation of RASFs and the production of MMPs, COX and prostaglandin E2 (PGE2) by RASFs. The proliferation of the RASFs stimulated with IL-1 beta 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-kappa B (NF-kappa B) 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-1 beta-stimulated RASFs, as well as the mRNA and protein expression of MMP-1, MMP-3, COX-2 and PGE2 induced by IL-1 beta. Kaempferol also inhibited the phosphorylation of ERK-1/2, p38 and JNK, as well as the activation of NF-kappa B induced by IL-1 beta. 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.