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    Novel identified aluminum hydroxide-induced pathways proof monocyte activation and pro-inflammatory preparedness.

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    Authors
    Kooijman, Sietske
    Brummelman, Jolanda
    van Els, Cécile A C M
    Marino, Fabio
    Heck, Albert J R
    Mommen, Geert P M
    Metz, Bernard
    Kersten, Gideon F A
    Pennings, Jeroen L A
    Meiring, Hugo D
    Type
    Article
    Language
    en
    
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    Title
    Novel identified aluminum hydroxide-induced pathways proof monocyte activation and pro-inflammatory preparedness.
    Published in
    J Proteomics 2018; 175:144-55
    Publiekssamenvatting
    Aluminum-based adjuvants are the most widely used adjuvants in human vaccines. A comprehensive understanding of the mechanism of action of aluminum adjuvants at the molecular level, however, is still elusive. Here, we unravel the effects of aluminum hydroxide Al(OH)3 by a systems-wide analysis of the Al(OH)3-induced monocyte response. Cell response analysis by cytokine release was combined with (targeted) transcriptome and full proteome analysis. Results from this comprehensive study revealed two novel pathways to become activated upon monocyte stimulation with Al(OH)3: the first pathway was IFNβ signaling possibly induced by DAMP sensing pathways like TLR or NOD1 activation, and second the HLA class I antigen processing and presentation pathway. Furthermore, known mechanisms of the adjuvant activity of Al(OH)3 were elucidated in more detail such as inflammasome and complement activation, homeostasis and HLA-class II upregulation, possibly related to increased IFNγ gene expression. Altogether, our study revealed which immunological pathways are activated upon stimulation of monocytes with Al(OH)3, refining our knowledge on the adjuvant effect of Al(OH)3 in primary monocytes.
    DOI
    10.1016/j.jprot.2017.12.021
    PMID
    29317357
    URI
    http://hdl.handle.net/10029/621164
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.jprot.2017.12.021
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