Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice.
Asbestos
Autoimmunity
Inflammation
LGM2605
Libby amphibole
Secoisolariciresinol diglucoside
Journal
Toxicology and applied pharmacology
ISSN: 1096-0333
Titre abrégé: Toxicol Appl Pharmacol
Pays: United States
ID NLM: 0416575
Informations de publication
Date de publication:
15 07 2019
15 07 2019
Historique:
received:
08
01
2019
revised:
16
04
2019
accepted:
21
04
2019
pubmed:
26
4
2019
medline:
16
5
2020
entrez:
26
4
2019
Statut:
ppublish
Résumé
Exposure to the Libby amphibole (LA) asbestos-like fibers found in Libby, Montana, is associated with inflammatory responses in mice and humans, and an increased risk of developing mesothelioma, asbestosis, pleural disease, and systemic autoimmune disease. Flaxseed-derived secoisolariciresinol diglucoside (SDG) has anti-inflammatory, anti-fibrotic, and antioxidant properties. We have previously identified potent protective properties of SDG against crocidolite asbestos exposure modeled in mice. The current studies aimed to extend those findings by evaluating the immunomodulatory effects of synthetic SDG (LGM2605) on LA-exposed mice. Male and female C57BL/6 mice were given LGM2605 via gavage initiated 3 days prior to and continued for 3 days after a single intraperitoneal dose of LA fibers (200 μg) and evaluated on day 3 for inflammatory cell influx in the peritoneal cavity using flow cytometry. LA exposure induced a significant increase (p < 0.0001) in spleen weight and peritoneal influx of white blood cells, all of which were reduced with LGM2605 with similar trends among males and females. Levels of peritoneal PMN cells were significantly (p < 0.0001) elevated post LA exposure, and were significantly (p < 0.0001) blunted by LGM2605. Importantly, LGM2605 significantly ameliorated the LA-induced mobilization of peritoneal B1a B cells. LGM2605 reduced LA-induced acute inflammation and WBC trafficking supporting its possible use in mitigating downstream LA fiber-associated diseases. Following acute exposure to Libby amphibole (LA) asbestos-like fibers, synthetic SDG (LGM2605), a small synthetic molecule, significantly reduced the LA-induced increase in spleen weight and peritoneal inflammation in C57BL/6 male and female mice. Our findings highlight that LGM2605 has immunomodulatory properties and may, thus, likely be a chemopreventive agent for LA-induced diseases.
Sections du résumé
BACKGROUND
Exposure to the Libby amphibole (LA) asbestos-like fibers found in Libby, Montana, is associated with inflammatory responses in mice and humans, and an increased risk of developing mesothelioma, asbestosis, pleural disease, and systemic autoimmune disease. Flaxseed-derived secoisolariciresinol diglucoside (SDG) has anti-inflammatory, anti-fibrotic, and antioxidant properties. We have previously identified potent protective properties of SDG against crocidolite asbestos exposure modeled in mice. The current studies aimed to extend those findings by evaluating the immunomodulatory effects of synthetic SDG (LGM2605) on LA-exposed mice.
METHODS
Male and female C57BL/6 mice were given LGM2605 via gavage initiated 3 days prior to and continued for 3 days after a single intraperitoneal dose of LA fibers (200 μg) and evaluated on day 3 for inflammatory cell influx in the peritoneal cavity using flow cytometry.
RESULTS
LA exposure induced a significant increase (p < 0.0001) in spleen weight and peritoneal influx of white blood cells, all of which were reduced with LGM2605 with similar trends among males and females. Levels of peritoneal PMN cells were significantly (p < 0.0001) elevated post LA exposure, and were significantly (p < 0.0001) blunted by LGM2605. Importantly, LGM2605 significantly ameliorated the LA-induced mobilization of peritoneal B1a B cells.
CONCLUSIONS
LGM2605 reduced LA-induced acute inflammation and WBC trafficking supporting its possible use in mitigating downstream LA fiber-associated diseases.
SUMMARY
Following acute exposure to Libby amphibole (LA) asbestos-like fibers, synthetic SDG (LGM2605), a small synthetic molecule, significantly reduced the LA-induced increase in spleen weight and peritoneal inflammation in C57BL/6 male and female mice. Our findings highlight that LGM2605 has immunomodulatory properties and may, thus, likely be a chemopreventive agent for LA-induced diseases.
Identifiants
pubmed: 31022494
pii: S0041-008X(19)30150-4
doi: 10.1016/j.taap.2019.04.018
pmc: PMC6582645
mid: NIHMS1529961
pii:
doi:
Substances chimiques
Asbestos, Amphibole
0
Butylene Glycols
0
Glucosides
0
LGM2605
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
81-93Subventions
Organisme : NCI NIH HHS
ID : R21 CA178654
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES023720
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA180548
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA133470
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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