Guglielmo Andrew, Sabra Adham, Elbery Mostafa, Cerveira Milena M, Ghenov Fernanda, Sunasee Rajesh, Ckless Karina
Department of Chemistry, State University of New York at Plattsburgh, Plattsburgh, NY, 12901, USA.
Department of Chemistry, State University of New York at Plattsburgh, Plattsburgh, NY, 12901, USA.
Chem Biol Interact. 2017 Aug 25;274:1-12. doi: 10.1016/j.cbi.2017.06.028. Epub 2017 Jun 30.
Recently we have demonstrated that needle-like cationic cellulose nanocrystals (CNC-AEMA2) evoke immunological responses through NLRP3 inflammasome/IL-1β inflammatory pathway. In this study we demonstrated that curcumin, a naturally occurring polyphenolic compound isolated from Curcuma longa (Zingiberaceae), was able to suppress, at least in part, this immunological response, as observed by diminished IL-1β secretion in CNC-AEMA2-stimulated macrophages primed with LPS. Curcumin is a well-known antioxidant and anti-inflammatory natural compound and in addition to acting as "scavenger" of reactive oxygen species (ROS), it can also upregulates antioxidant enzymes. However, the mechanisms by which this natural compound exerts its protective activity is still under investigation. We hypothesize that curcumin may also affect S-glutathionylation of key proteins involved in the NLRP3 inflammasome/IL-1β pathway, and therefore impact their protein-protein interactions. The goal of this study was to investigate the effects of curcumin on the S-glutathionylation of NLRP3 induced by CNC-AEMA2 in LPS-primed mouse macrophages (J774A.1), as well as interactions among proteins of the NLRP3 inflammasome complex. Our main finding indicates that the addition of curcumin concomitantly with LPS caused the greatest decrease in NLRP3 S-glutathionylation and a respective increase in caspase-1 S-glutathionylation, which appears to favor protein-protein interactions in the NLRP3 complex. Taking together, our results suggest that, at least in part, the anti-inflammatory activity of curcumin is associated with changes in S-glutathionylation of key NLRP3 inflammasome components, and perhaps resulting in sustained complex assembly and suppression of IL-1β secretion.
最近我们已经证明，针状阳离子纤维素纳米晶体（CNC-AEMA2）通过NLRP3炎性小体/IL-1β炎症途径引发免疫反应。在本研究中，我们证明了姜黄素，一种从姜科植物姜黄中分离出的天然多酚化合物，能够至少部分抑制这种免疫反应，如在LPS预处理的巨噬细胞中，经CNC-AEMA2刺激后IL-1β分泌减少所观察到的那样。姜黄素是一种著名的抗氧化和抗炎天然化合物，除了作为活性氧（ROS）的“清除剂”外，它还能上调抗氧化酶。然而，这种天然化合物发挥其保护活性的机制仍在研究中。我们假设姜黄素也可能影响参与NLRP3炎性小体/IL-1β途径的关键蛋白的S-谷胱甘肽化，从而影响它们的蛋白质-蛋白质相互作用。本研究的目的是研究姜黄素对LPS预处理的小鼠巨噬细胞（J774A.1）中CNC-AEMA2诱导的NLRP3的S-谷胱甘肽化的影响，以及NLRP3炎性小体复合物中蛋白质之间的相互作用。我们的主要发现表明，与LPS同时添加姜黄素导致NLRP3 S-谷胱甘肽化的最大程度降低和caspase-1 S-谷胱甘肽化相应增加，这似乎有利于NLRP3复合物中的蛋白质-蛋白质相互作用。综上所述，我们的结果表明，至少部分地，姜黄素的抗炎活性与关键NLRP3炎性小体成分的S-谷胱甘肽化变化有关，并且可能导致持续的复合物组装和IL-1β分泌的抑制。
