Cheng Bin-Feng, Gao Yao-Xin, Lian Jun-Jiang, Guo Dan-Dan, Liu Tong-Tong, Xie Yun-Fei, Wang Lei, Yang Hai-Jie, Wang Mian, Feng Zhi-Wei
School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang 453003, Henan, China.
School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang 453003, Henan, China.
Int Immunopharmacol. 2017 Sep;50:224-229. doi: 10.1016/j.intimp.2017.06.032. Epub 2017 Jul 10.
The present study shows the basis for the anti-inflammatory effects of pitavastatin in interleukin (IL)-1β-induced human synovial cells. The SW982 cells were pretreated with pitavastatin at different concentrations (5μM and 10μM), followed by IL-1β (10ng/mL) stimulation. The results showed that pitavastatin inhibited the expression of inflammatory mediators IL-6 and IL-8. Furthermore, pitavastatin inhibited the phosphorylation of p38, extracellular signal-related kinase (ERK), c-jun N-terminal kinase (JNK) and protein kinase B (Akt). It also suppressed the degradation of I kappa B alpha and blocked p65 translocation into the nucleus. These findings suggest that the mechanism underlying the inhibitory effects of pitavastatin on IL-1β-induced IL-6 and IL-8 release might be mediated by the suppression of mitogen-activated protein kinase (MAPK), Akt, and nuclear factor-κB (NF-κB) signaling pathways. These results may also indicate that pitavastatin may be potentially utilized as an effective therapeutic agent for the treatment of osteoarthritis.
本研究揭示了匹伐他汀在白细胞介素（IL）-1β诱导的人滑膜细胞中发挥抗炎作用的机制。将SW982细胞用不同浓度（5μM和10μM）的匹伐他汀预处理，随后用IL-1β（10ng/mL）刺激。结果显示，匹伐他汀抑制炎症介质IL-6和IL-8的表达。此外，匹伐他汀抑制p38、细胞外信号调节激酶（ERK）、c-Jun氨基末端激酶（JNK）和蛋白激酶B（Akt）的磷酸化。它还抑制IκBα的降解并阻止p65易位至细胞核。这些发现表明，匹伐他汀对IL-1β诱导的IL-6和IL-8释放的抑制作用机制可能是通过抑制丝裂原活化蛋白激酶（MAPK）、Akt和核因子κB（NF-κB）信号通路介导的。这些结果还可能表明，匹伐他汀可能有潜力用作治疗骨关节炎的有效治疗药物。
