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Toxicol Appl Pharmacol. 2019 Jul 15;375:81-93. doi: 10.1016/j.taap.2019.04.018. Epub 2019 Apr 23.

Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice.

Author information

1
Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 3450 Hamilton Walk, Stemmler Hall, Office Suite 227, Philadelphia, PA 19104, United States of America. Electronic address: melpo@pennmedicine.upenn.edu.
2
Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 3450 Hamilton Walk, Stemmler Hall, Office Suite 227, Philadelphia, PA 19104, United States of America. Electronic address: ralphp@pennmedicine.upenn.edu.
3
Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 3450 Hamilton Walk, Stemmler Hall, Office Suite 227, Philadelphia, PA 19104, United States of America. Electronic address: kyewpark@pennmedicine.upenn.edu.
4
Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 3450 Hamilton Walk, Stemmler Hall, Office Suite 227, Philadelphia, PA 19104, United States of America. Electronic address: albelda@pennmedicine.upenn.edu.
5
Department of Biological Sciences, Life Sciences 207, Idaho State University, Pocatello, ID 83209, United States of America. Electronic address: servkint@isu.edu.
6
Department of Microbiology and Immunology, Montana State University, Health Sciences Building Rm 133, PO Box 173610, Bozeman, MT 59717, United States of America. Electronic address: deborah.keil@montana.edu.
7
Department of Microbiology and Immunology, Montana State University, Health Sciences Building Rm 133, PO Box 173610, Bozeman, MT 59717, United States of America. Electronic address: jean.pfau@montana.edu.

Abstract

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.

KEYWORDS:

Asbestos; Autoimmunity; Inflammation; LGM2605; Libby amphibole; Secoisolariciresinol diglucoside

PMID:
31022494
PMCID:
PMC6582645
[Available on 2020-07-15]
DOI:
10.1016/j.taap.2019.04.018

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