Quercetin and HSC70 coregulate the anti-inflammatory action of the ubiquitin-like protein MNSFβ
Quercetin and HSC70 coregulate the anti-inflammatory action of the ubiquitin-like protein MNSFβ
复制标题
DOI：
10.1007/s11033-021-06949-y
复制
发表时间：
2021-11-12
影响因子：
2.8
通讯作者：
Kono，Megumi
中科院分区：
文献类型：
--
作者：
Nakamura，Morihiko;Fukuma，Yuki;Kono，Megumi
背景栎素是一种黄酮醇，可以改变许多细胞过程。单克隆性非特异性抑制因子β是泛素样蛋白家族中的一员，参与多种生物学过程。已有研究表明，在脂多糖刺激的巨噬细胞中，槲皮素可调节MNSFβ对肿瘤坏死因子α分泌的影响。本研究发现，槲皮素和热休克蛋白HSC70共同调节巨噬细胞因子β的作用。方法与结果在巨噬细胞样细胞系Raw264.7中，栎皮素呈剂量依赖性抑制γ/干扰素诱导的一氧化氮的产生，而不产生细胞毒性。SiRNA抑制实验表明，在脂多糖刺激的Raw264.7细胞中，Quercetin抑制了MNSFRNA和HSC70siRNA介导的肿瘤坏死因子β和C-C趋化因子超家族成员RANTES的产生。Western印迹分析表明，栎素和HSC70通过影响MNSFκα和促凋亡蛋白BclG的复合体的形成，调节ERK1/2的激活和内毒素刺激的I NSFBβ的降解。MNSFHSC70参与TLR4/MYD88信号转导，但不参与TLR3信号转导。结论β是促进MNSFHSC70稳定的重要分子伴侣。槲皮素可能通过调节分子伴侣β的作用来负向调控MNSFHSC70的功能。MNSFβ介导TLR4/MYD88信号转导，但不介导TLR3信号转导。
BackgroundQuercetin is a flavonol that modifies many cellular processes. Monoclonal nonspecific suppressor factor β is a member of the ubiquitin-like family of proteins that are involved in various biological processes. It has been demonstrated that quercetin regulates the effect of MNSFβ on tumor necrosis factor-α secretion in lipopolysaccharide (LPS)-stimulated macrophages. This study found that quercetin and the heat shock protein HSC70 coregulate the action of MNSFβ.Methods and resultsQuercetin dose-dependently suppressed the LPS/interferon γ-induced nitric oxide production without cytotoxicity in the macrophage-like cell line Raw264.7. SiRNA knockdown experiments showed that quercetin inhibited the MNSFβ and HSC70 siRNA-mediated enhancement of TNFα and the production of RANTES, a member of C–C chemokine superfamily, in LPS-stimulated Raw264.7 cells. Western blot analysis showed that quercetin and HSC70 regulated ERK1/2 activation and LPS-stimulated IκBα degradation by affecting the complex formation of MNSFβ and the proapoptotic protein Bcl-G. Moreover, MNSFβ is implicated in TLR4/MyD88 signaling but not in TLR3 signaling.ConclusionsHSC70 is an important chaperone that facilitates the stabilization of MNSFβ. Quercetin may negatively control the function of MNSFβ by regulating the action of the molecular chaperone HSC70. MNSFβ mediates TLR4/Myd88 signaling but not TLR3 signaling.