Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, PR China; Collaborative Innovation Center of Biomedicine for Public Hygiene Emergency and Critical Care, Jiangsu Life Sciences & Technology Innovation Park, Nanjing, Jiangsu, PR China.
Int Immunopharmacol. 2014 Jan;18(1):12-9. doi: 10.1016/j.intimp.2013.10.021. Epub 2013 Nov 4.
Extracellular polysaccharides (EPSs) are high-molecular weight sugar-based polymers that are synthesized and secreted by many microorganisms. Recently, EPSs have attracted particular attention due to their multiple biological functions including anti-inflammation. However, studies rarely reported the molecular mechanisms underlying their functions. We previously purified an EPS from an oligotrophic bacteria (Bacillus sp. LBP32) found in Lop Nur Desert, which possesses a potent antioxidant activity, while the anti-inflammatory effects of EPS and signaling mechanisms underlying its action have not been clarified. In this study, we demonstrated that EPS significantly inhibited the LPS-induced release of pro-inflammatory mediators, such as nitric oxide (NO), IL-6 and TNF-α, without any significant cytotoxicity. EPS also downregulated the expression of nitric oxide synthase (iNOS) induced by LPS. Furthermore, activation of nuclear factor κB (NF-κB) was abrogated by EPS through inhibited the phosphorylation of IκB kinase (IKK). Activations of Mitogen-activated protein kinases (MAPKs), including p38 MAPK and c-Jun N-terminal kinase (JNK), were also found to be inhibited by EPS. In addition, the level of intracellular reactive oxygen species (ROS) was also significantly decreased with the treatment of EPS. In vivo experiments were conducted and showed that EPS could greatly improve the outcome of mice with LPS-induced endotoxic shock. Taken together, our data indicate that EPS prevents LPS-induced inflammatory response by inhibiting NF-κB and MAPKs activation and ROS production.
胞外多糖（EPSs）是由许多微生物合成和分泌的高分子量糖基聚合物。最近，由于其具有多种生物学功能，包括抗炎作用，EPS 引起了特别关注。然而，研究很少报道其功能的分子机制。我们之前从位于罗布泊沙漠的贫营养细菌（芽孢杆菌 LBP32）中纯化了一种 EPS，它具有很强的抗氧化活性，而 EPS 的抗炎作用及其作用的信号机制尚未阐明。在这项研究中，我们证明 EPS 可显著抑制 LPS 诱导的促炎介质（如一氧化氮（NO）、IL-6 和 TNF-α）的释放，同时没有明显的细胞毒性。EPS 还下调了 LPS 诱导的一氧化氮合酶（iNOS）的表达。此外，EPS 通过抑制 IκB 激酶（IKK）的磷酸化来抑制核因子 κB（NF-κB）的激活。MAPK 中的丝裂原激活蛋白激酶（MAPKs）的激活，包括 p38 MAPK 和 c-Jun N-末端激酶（JNK），也被发现被 EPS 抑制。此外，EPS 处理还显著降低了细胞内活性氧（ROS）的水平。体内实验表明，EPS 可以极大地改善 LPS 诱导的内毒素休克小鼠的预后。综上所述，我们的数据表明，EPS 通过抑制 NF-κB 和 MAPKs 的激活以及 ROS 的产生来防止 LPS 诱导的炎症反应。
