Tong Wenzhi, Chen Xiangxiu, Song Xu, Chen Yaqin, Jia Renyong, Zou Yuanfeng, Li Lixia, Yin Lizi, He Changliang, Liang Xiaoxia, Ye Gang, Lv Cheng, Lin Juchun, Yin Zhongqiong
Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, P.R. China.
Exp Ther Med. 2020 Mar;19(3):1824-1834. doi: 10.3892/etm.2019.8396. Epub 2019 Dec 31.
Resveratrol (Res) is a natural compound that possesses anti-inflammatory properties. However, the protective molecular mechanisms of Res against lipopolysaccharide (LPS)-induced inflammation have not been fully studied. In the present study, RAW264.7 cells were stimulated with LPS in the presence or absence of Res, and the subsequent modifications to the LPS-induced signaling pathways caused by Res treatment were examined. It was identified that Res decreased the mRNA levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein MyD88, TIR domain-containing adapter molecule 2, which suggested that Res may inhibit the activation of the TLR4 signaling pathway. It suppressed the expression levels of total and phosphorylated TLR4, NF-κB inhibitor, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase, extracellular signal-regulated kinase 1/2 and interferon (IFN) regulatory factor 3 (IRF3) proteins. Following treatment with Res or specific inhibitors, the production of pro-inflammatory mediators including tumor necrosis factor-α, interleukin (IL)-6, IL-8 and IFN-β were decreased and the expression of anti-inflammatory mediator IL-10 was increased. These results suggested that Res may inhibit the signaling cascades of NF-κB, MAPKs and IRF3, which modulate pro-inflammatory cytokines. In conclusion, Res exhibited a therapeutic effect on LPS-induced inflammation through suppression of the TLR4-NF-κB/MAPKs/IRF3 signaling cascades.
白藜芦醇（Res）是一种具有抗炎特性的天然化合物。然而，Res对脂多糖（LPS）诱导的炎症的保护分子机制尚未得到充分研究。在本研究中，在有或无Res的情况下用LPS刺激RAW264.7细胞，并检测Res处理对LPS诱导的信号通路的后续修饰。结果发现，Res降低了Toll样受体4（TLR4）、髓样分化初级反应蛋白MyD88、含TIR结构域的衔接分子2的mRNA水平，这表明Res可能抑制TLR4信号通路的激活。它抑制了总TLR4、磷酸化TLR4、NF-κB抑制剂、p38丝裂原活化蛋白激酶（MAPK）、c-Jun氨基末端激酶、细胞外信号调节激酶1/2和干扰素（IFN）调节因子3（IRF3）蛋白的表达水平。用Res或特异性抑制剂处理后，包括肿瘤坏死因子-α、白细胞介素（IL）-6、IL-8和IFN-β在内的促炎介质的产生减少，抗炎介质IL-10的表达增加。这些结果表明，Res可能抑制调节促炎细胞因子的NF-κB、MAPKs和IRF3的信号级联反应。总之，Res通过抑制TLR4-NF-κB/MAPKs/IRF3信号级联反应对LPS诱导的炎症具有治疗作用。
