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Int Forum Allergy Rhinol. 2017 Feb;7(2):177-184. doi: 10.1002/alr.21865. Epub 2016 Nov 11.

Prevention of sinonasal inflammation by a synthetic glycosaminoglycan.

Author information

1
Division of Head and Neck Surgery, Rhinology-Sinus and Skull Base Surgery Program, Department of Surgery; University of Utah School of Medicine, Salt Lake City, UT.
2
GlycoMira Therapeutics, Inc., Salt Lake City, UT.
3
Department of Medicinal Chemistry and Center for Therapeutic Biomaterials, Salt Lake City, UT.
4
Division of Pediatric Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT.

Abstract

BACKGROUND:

Glycosaminoglycans (GAGs) are polysaccharides that are distributed on respiratory epithelial cells, endothelial cells, and submucosal glands. Uniquely positioned, certain GAGs exhibit anti-inflammatory properties in respiratory diseases and serve important roles in repairing mucosal surfaces and modulating mucociliary clearance. We hypothesized that topical administration of a synthetic GAG (GM-0111) would prevent sinonasal inflammation in a mouse model of rhinosinusitis (RS).

METHODS:

To test our hypothesis, C57BL/6 mice were intranasally administered fluorescent GM-0111, and sinonasal tissues were examined for coating and penetration ability. To test therapeutic feasibility, mice (n = 6) were given GM-0111 or hyaluronic acid (HA; 800 μg dose) prior to inducing RS with inflammatory molecule LL-37 (115 μg dose). After 24 hours, sinonasal tissues were harvested for histological and biochemical analysis of inflammatory markers (inflammatory cell infiltration, lamina propria [LP] thickening, and neutrophil enzyme myeloperoxidase [MPO]) and cell death.

RESULTS:

GM-0111 was observed within sinonasal tissues 1 hour and 24 hours after intranasal administration, indicating rapid and effective coating and penetration. GM-0111 prevented sinonasal tissues from developing inflammatory changes, with significant reductions in mast cell infiltration (p < 0.05), LP thickening (p < 0.001), and MPO levels (p < 0.01) when compared to tissues treated with LL-37 and those pretreated with HA. GM-0111 reduced cell death within sinonasal tissues in contrast to LL-37-treated tissues.

CONCLUSION:

We report a new synthetic GAG (GM-0111) that uniformly coats and penetrates into the sinonasal mucosa to prevent sinonasal inflammation and cell death in a mouse model of RS.

KEYWORDS:

anti-inflammatory therapeutic; cathelicidin; immune response; rhinosinusitis; sulfated glycosaminoglycan

PMID:
27863138
PMCID:
PMC5299046
DOI:
10.1002/alr.21865
[Indexed for MEDLINE]
Free PMC Article

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