title: A steroid-mimicking nanomaterial that mediates inhibition of human lung mast cell responses.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Luna nanoWorks Division, Luna Innovations Inc., Danville, VA, USA; University of North Carolina Greensboro, Joint School of Nanoscience and Nanoengineering, Greensboro, NC, USA.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Dellinger
authors.affiliation: Luna nanoWorks Division, Luna Innovations Inc., Danville, VA, USA.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: University of North Carolina Greensboro, Joint School of Nanoscience and Nanoengineering, Greensboro, NC, USA. Electronic address: clkepley@uncg.edu.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Kepley
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy; D015550:Cell Degranulation / Q000187:drug effects; D037741:Fullerenes / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D037741:Fullerenes; D013256:Steroids; C069836:fullerene C70
keywords: Dual-specificity phosphatase one; Fullerenes; Inhaled corticosteroids; Mast cell