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Nanomedicine. 2014 Aug;10(6):1185-93. doi: 10.1016/j.nano.2014.02.006. Epub 2014 Feb 22.

A steroid-mimicking nanomaterial that mediates inhibition of human lung mast cell responses.

Author information

1
Luna nanoWorks Division, Luna Innovations Inc., Danville, VA, USA; University of North Carolina Greensboro, Joint School of Nanoscience and Nanoengineering, Greensboro, NC, USA.
2
Luna nanoWorks Division, Luna Innovations Inc., Danville, VA, USA.
3
University of North Carolina Greensboro, Joint School of Nanoscience and Nanoengineering, Greensboro, NC, USA. Electronic address: clkepley@uncg.edu.

Abstract

Water-soluble fullerenes can be engineered to regulate activation of mast cells (MC) and control MC-driven diseases in vivo. To further understand their anti-inflammatory mechanisms a C70-based fullerene conjugated to four myo-inositol molecules (C70-I) was examined in vitro for its effects on the signaling pathways leading to mediator release from human lung MC. The C70-I fullerene stabilizes MC and acts synergistically with long-acting β2-adrenergic receptor agonists (LABA) to enhance inhibition of MC mediator release through FcεRI-simulation. The inhibition was paralleled by the upregulation of dual-specificity phosphatase one (DUSP1) gene and protein levels. Concomitantly, increases in MAPK were blunted in C70-I treated cells. The increase in DUSP1 expression was due to the ability of C70-I to prevent the ubiquitination and degradation of DUSP1. These findings identify a mechanism of how fullerenes inhibit inflammatory mediator release from MC and suggest they could potentially be an alternative therapy for steroid resistant asthmatics.

FROM THE CLINICAL EDITOR:

This study investigates the role and mechanism of action of fullerenes in deactivating mast cell-based inflammation, paving the way to the development of a novel, non-steroid therapy in reactive airway disease.

KEYWORDS:

Dual-specificity phosphatase one; Fullerenes; Inhaled corticosteroids; Mast cell

PMID:
24566277
PMCID:
PMC4119857
DOI:
10.1016/j.nano.2014.02.006
[Indexed for MEDLINE]
Free PMC Article

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