Title: The Synthetic Lignan Secoisolariciresinol Diglucoside Prevents Asbestos-Induced NLRP3 Inflammasome Activation in Murine Macrophages.
Authors: Pietrofesa, Ralph A; Woodruff, Patrick; Hwang, Wei-Ting; Patel, Priyal; Chatterjee, Shampa; Albelda, Steven M; Christofidou-Solomidou, Melpo
Published In Oxid Med Cell Longev, (2017)
Abstract: The interaction of asbestos with macrophages drives two key processes that are linked to malignancy: (1) the generation of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and (2) the activation of an inflammation cascade that drives acute and chronic inflammation, with the NLRP3 inflammasome playing a key role. Synthetic secoisolariciresinol diglucoside (SDG), LGM2605, is a nontoxic lignan with anti-inflammatory and antioxidant properties and was evaluated for protection from asbestos in murine peritoneal macrophages (MF).MFs were exposed to crocidolite asbestos ± LGM2605 given 4 hours prior to exposure and evaluated at various times for NLRP3 expression, secretion of inflammasome-activated cytokines (IL-1β and IL-18), proinflammatory cytokines (IL-6, TNFα, and HMGB1), NF-κB activation, and levels of total nitrates/nitrites.Asbestos induces a significant (p < 0.0001) increase in the NLRP3 subunit, release of proinflammatory cytokines, NLRP3-activated cytokines, NF-κB, and levels of nitrates/nitrites. LGM2605 significantly reduced NLRP3 ranging from 40 to 81%, IL-1β by 89-96%, and TNFα by 67-78%, as well as activated NF-κB by 48-49% while decreasing levels of nitrates/nitrites by 85-93%.LGM2605 reduced asbestos-induced NLRP3 expression, proinflammatory cytokine release, NF-κB activation, and nitrosative stress in MFs supporting its possible use in preventing the asbestos-induced inflammatory cascade leading to malignancy.
PubMed ID: 29075366
MeSH Terms: Animals; Asbestos/adverse effects*; Butylene Glycols/pharmacology; Butylene Glycols/therapeutic use*; Glucosides/pharmacology; Glucosides/therapeutic use*; Inflammasomes/adverse effects*; Macrophages/metabolism*; Mice; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*