The Synthetic Lignan Secoisolariciresinol Diglucoside Prevents Asbestos-Induced NLRP3 Inflammasome Activation in Murine Macrophages

Background. 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). Methods. 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-1 beta and IL-18), proinflammatory cytokines (IL-6, TNF alpha, and HMGB1), NF-kappa B activation, and levels of total nitrates/nitrites. Results. Asbestos induces a significant (p < 0.0001) increase in the NLRP3 subunit, release of proinflammatory cytokines, NLRP3-activated cytokines, NF-kappa B, and levels of nitrates/nitrites. LGM2605 significantly reduced NLRP3 ranging from 40 to 81%, IL-1 beta by 89-96%, and TNF alpha by 67-78%, as well as activated NF-kappa B by 48-49% while decreasing levels of nitrates/nitrites by 85-93%. Conclusions. LGM2605 reduced asbestos-induced NLRP3 expression, proinflammatory cytokine release, NF-kappa B activation, and nitrosative stress in MFs supporting its possible use in preventing the asbestos-induced inflammatory cascade leading to malignancy.