Department of Orthopedic Surgery, Liaocheng People's Hospital, Liaocheng, China.
Dongchang Fu People's Hospital, Liaocheng, China.
Scand J Immunol. 2019 Aug;90(2):e12773. doi: 10.1111/sji.12773. Epub 2019 May 22.
It has been reported that vitexin has anti-inflammatory effects in osteoarthritis (OA) rats. However, the effects of vitexin on interleukins-1β (IL-1β)-stimulated OA patient-derived chondrocytes have not been reported. The purpose of this study was to investigate the anti-inflammatory effects of vitexin on IL-1β-stimulated human osteoarthritis chondrocytes and to reveal the involvement of hypoxia-inducible factor 1α (HIF-1α) pathway. Enzyme-linked immunosorbent assay, quantitative real-time PCR and Western blotting assays were employed. ELISA results demonstrated that the proinflammatory cytokine levels of interleukins-6 (IL-6) and tumour necrosis factor α (TNF-α) in the serum and synovial fluid and HIF-1α level in the synovial fluid were significantly elevated in OA patients compared to normal healthy subjects. Moreover, the Western blotting results indicated that the protein expression of HIF-1α was significantly higher in the cartilage tissues of OA patients. OA patient-derived chondrocytes were stimulated by IL-1β and treated with different concentration of vitexin for 24 hours. Vitexin showed no cytotoxicity and increased the survival of chondrocytes under IL-1β stimulation. Vitexin suppressed IL-1β-induced production of NO and prostaglandin E2 (PGE ) in chondrocytes culture. The treatment of vitexin significantly inhibited IL-1β-induced expressions of proinflammatory cytokine levels of IL-6, TNF-α, matrix metalloproteinase (MMP)-1, MMP-3 and MMP-13. Furthermore, Western blotting results demonstrated that HIF-1α is involved in vitexin's protective effects on IL-1β-stimulated injuries in OA patient-derived chondrocytes. Our study demonstrates that vitexin alleviates IL-1β-induced inflammatory responses in chondrocytes from osteoarthritis patients, which may be attributed partly to the inhibition of HIF-1α pathway.
据报道，牡荆素在骨关节炎（OA）大鼠中具有抗炎作用。然而，牡荆素对白细胞介素-1β（IL-1β）刺激的 OA 患者来源软骨细胞的影响尚未报道。本研究旨在探讨牡荆素对 IL-1β刺激的人 OA 软骨细胞的抗炎作用，并揭示缺氧诱导因子 1α（HIF-1α）通路的参与。采用酶联免疫吸附试验、实时定量 PCR 和 Western blot 检测。ELISA 结果表明，与正常健康受试者相比，OA 患者血清和滑液中促炎细胞因子白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）水平以及滑液中 HIF-1α 水平显著升高。此外，Western blot 结果表明，OA 患者软骨组织中 HIF-1α 的蛋白表达明显升高。用 IL-1β刺激 OA 患者来源的软骨细胞，并给予不同浓度的牡荆素处理 24 小时。牡荆素在 IL-1β 刺激下对软骨细胞无细胞毒性作用，并提高软骨细胞的存活率。牡荆素抑制软骨细胞中一氧化氮（NO）和前列腺素 E2（PGE2）的产生。牡荆素治疗可显著抑制 IL-1β诱导的促炎细胞因子白细胞介素 6、TNF-α、基质金属蛋白酶（MMP）-1、MMP-3 和 MMP-13 的表达。此外，Western blot 结果表明，HIF-1α 参与牡荆素对 OA 患者来源软骨细胞中 IL-1β 刺激损伤的保护作用。本研究表明，牡荆素减轻了 IL-1β 诱导的 OA 患者软骨细胞炎症反应，这可能部分归因于对 HIF-1α 通路的抑制。
