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

作者：Dellinger Anthony L; Zhou Zhiguo; Kepley Christopher L^*

来源：Nanomedicine: Nanotechnology, Biology and Medicine , 2014, 10(6): 1185-1193.

DOI：10.1016/j.nano.2014.02.006

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

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 C-70-based fullerene conjugated to four myo-inositol molecules (C-70-I) was examined in vitro for its effects on the signaling pathways leading to mediator release from human lung MC. The C-70-I fullerene stabilizes MC and acts synergistically with long-acting beta(2)-adrenergic receptor agonists (LABA) to enhance inhibition of MC mediator release through Fc epsilon RI-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 C-70-I treated cells. The increase in DUSP1 expression was due to the ability of C-70-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.

• 出版日期2014-8