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• W2794414314 endingPage "e0193499" @default.
• W2794414314 startingPage "e0193499" @default.
• W2794414314 abstract "Mast cells represent a crucial cell type in host defense; however, maladaptive responses are contributing factors in the pathogenesis of allergic diseases. Previous work in our laboratory has shown that exposure to silver nanoparticles (AgNPs) results in mast cell degranulation via a non-immunoglobulin E (IgE) mechanism. In this study, we utilized a systems biology approach to identify novel genetic factors playing a role in AgNP-induced mast cell degranulation compared to the classical activation by antigen-mediated FcεRI crosslinking. Mast cell degranulation was assessed in bone marrow-derived mast cells isolated from 23 strains of mice following exposure to AgNPs or FcεRI crosslinking with dinitrophenyl (DNP). Utilizing strain-dependent mast cell degranulation, an association mapping study identified 3 chromosomal regions that were significantly associated with mast cell degranulation by AgNP and one non-overlapping region associated with DNP-mediated degranulation. Two of the AgNP-associated regions correspond to genes previously reported to be associated with allergic disorders (Trac2 on chromosome 1 and Traf6 on chromosome 2) and an uncharacterized gene identified on chromosome 1 (Fam126b). In conjunction, RNA-sequencing performed on mast cells from the high and low responder strains revealed 3754 and 34 differentially expressed genes that were unique to DNP and AgNP exposures, respectively. Select candidate genes include Ptger4, a gene encoding a G-protein coupled receptor in addition to a multifunctional adaptor protein, Txnip, that may be driving mast cell degranulation by AgNP. Taken together, we identified novel genes that have not been previously shown to play a role in nanoparticle-mediated mast cell activation. With further functional evaluation in the future, these genes may be potential therapeutic targets in the treatment of non-IgE mediated mast cell-linked disorders." @default.
• W2794414314 created "2018-03-29" @default.
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• W2794414314 creator A5087948456 @default.
• W2794414314 date "2018-03-22" @default.
• W2794414314 modified "2023-10-09" @default.
• W2794414314 title "Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms" @default.
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• W2794414314 doi "https://doi.org/10.1371/journal.pone.0193499" @default.
• W2794414314 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5863960" @default.
• W2794414314 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29566008" @default.
• W2794414314 hasPublicationYear "2018" @default.
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