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

Abstract

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-1β and IL-18), proinflammatory cytokines (IL-6, TNFα, and HMGB1), NF-κB 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-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%.

CONCLUSIONS:

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.

• Authors: Ralph A Pietrofesa, Patrick Woodruff, Wei-Ting Hwang, Priyal Patel, Shampa Chatterjee, Steven M Albelda, Melpo Christofidou-Solomidou
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2017 Pg. 7395238 ( 2017) ISSN: 1942-0994 [Electronic] United States
• PMID: 29075366 (Publication Type: Journal Article)

Chemical References

• Butylene Glycols
• Glucosides
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Asbestos
• secoisolariciresinol diglucoside

Topics

• Animals
• Asbestos (adverse effects)
• Butylene Glycols (pharmacology, therapeutic use)
• Glucosides (pharmacology, therapeutic use)
• Inflammasomes (adverse effects)
• Macrophages (metabolism)
• Mice
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)