A new steroid-mimicking nanomaterial that mediates inhibition of human lung mast cells responses

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Anthony Dellinger (Creator)
Christopher Kepley, Associate Professor (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.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 ß2-adrenergic receptor agonists (LABA) to enhance inhibition of MC mediator release through FcepsilonRI-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.

Additional Information

Publication
Nanomedicine: Nanotechnology, Biology and Medicine, 2014 Aug;10(6):1185-93.
Language: English
Date: 2014
Keywords
Fullerenes, Inhaled corticosteroids, Mast cell, Dual-specificity phosphatase one

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