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 and IL-18), proinflammatory cytokines (IL-6, TNF, and HMGB1), NF-B activation, and levels of total nitrates/nitrites.

RESULTS

Asbestos induces a significant ( < 0.0001) increase in the NLRP3 subunit, release of proinflammatory cytokines, NLRP3-activated cytokines, NF-B, and levels of nitrates/nitrites. LGM2605 significantly reduced NLRP3 ranging from 40 to 81%, IL-1 by 89-96%, and TNF by 67-78%, as well as activated NF-B by 48-49% while decreasing levels of nitrates/nitrites by 85-93%.

CONCLUSIONS

LGM2605 reduced asbestos-induced NLRP3 expression, proinflammatory cytokine release, NF-B activation, and nitrosative stress in MFs supporting its possible use in preventing the asbestos-induced inflammatory cascade leading to malignancy.