Role and mechanism of ROS scavengers in alleviating NLRP3‐mediated inflammation

Abstract

Inflammation, as a common immune response to various infections or injuries, can cause many dangerous and complicated diseases. Inflammasome is a protein complex playing a vital role in an inflammation process, and the nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome has been the most-widely studied one. Recent evidence suggests the reactive oxygen species (ROS)-NLRP3 signaling pathway to be a possible NLRP3 inflammasome regulation model. Numerous recent preclinical reports indicate that application of antioxidants could scavenge excessive ROS and attenuate inflammatory responses through suppressing NLRP3 inflammasome activation. This article, at first, briefly overviews how ROS may mediate the regulation of NLRP3 inflammasome activation. Then, preclinical researches of various ROS scavengers for treating NLRP3 inflammasome-associated diseases are focused on and critically analyzed. Finally, the potential of antioxidant treatment as a therapy for inflammation is to be discussed, and perspectives on future research directions will be shared.

Autophagy and its significance in periodontal disease

“…42 High levels of mitochondrial ROS production which damage the cell integrity and function have been shown in patients with periodontitis and a reduction in autophagosome formation was observed after ROS enhancement in HGFs. 32,81 Consistent with previous findings, ROS induction by the autophagic inhibitor 3-MA contributed to NLRP3 inflammasome activation and increased IL-1β production. 82,83 Another study showed that induction of autophagy decreased ROS accumulation in LPS-stimulated HGFs.…”

“…Furthermore, inhibition of autophagy significantly increased IL‐1β release and NLR family pyrin domain containing 3 (NLRP3) inflammasome formation, suggesting that autophagy limited the P.g‐induced inflammatory response 42 . High levels of mitochondrial ROS production which damage the cell integrity and function have been shown in patients with periodontitis and a reduction in autophagosome formation was observed after ROS enhancement in HGFs 32,81 . Consistent with previous findings, ROS induction by the autophagic inhibitor 3‐MA contributed to NLRP3 inflammasome activation and increased IL‐1β production 82,83 .…”

Eucalyptol alleviates inflammation and pain responses in a mouse model of gout arthritis

“…We further investigated the mechanisms underlying NLRP3 inflammasome inhibition by eucalyptol. Evidence suggests that ROS generation activates NLRP3 inflammasome, whereas ROS scavengers block NLRP3 inflammasome activation (Sho & Xu, ; Zhou, Yazdi, Menu, & Tschopp, ). MSU induces NLRP3 activation via ROS‐dependent manner (Zhou, Tardivel, Thorens, Choi, & Tschopp, ).…”

Gut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic Target

“…Activation of the TMAO-induced endothelial NLRP3 inflammasome was reduced by a mitochondrial ROS scavenger or SIRT3 overexpression in human umbilical vein endothelial cells (HUVECs), which suggested that the activation was mediated in part by inhibition of the SIRT3-SOD2-mtROS signaling pathway (Chen et al, 2017). Other studies proposed that this activation was mediated by the ROS-TXNIP pathway (Zhou et al, 2010; Sho and Xu, 2019). TXNIP is the most widely studied protein which links ROS and NLRP3 inflammasome (Zhou et al, 2010; Lane et al, 2013; Ye et al, 2017).…”