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Title
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MUTZ-3-derived dendritic cells as an in vitro alternative model to progenitor-derived dendritic cells for testing of chemical sensitizers
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Author
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Abstract
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| The cytokine-dependent CD34+ human acute myeloid leukaemia cell line MUTZ-3 was used to generate immature dendritic-like cells (MUTZ-3 DC) and their validity as an alternative to primary CD34+ progenitor-derived DC (CD34DC) for testing chemical-induced sensitization was assessed. Expression levels of the DC maturation markers HLA-DR, CD86, CD83 and CD11c were studied using flow cytometry after 24 and 48 h exposure to the model compound nickel sulphate (100 and 300 μM). No maturation of MUTZ-3 DC was observed, whereas significantly upregulated expression levels of CD83 and CD86 were noticed in CD34DC after 24 h treatment with 300 μM nickel sulphate compared to control cells. Differential expression of the cytokine genes IL1β, IL6, IL8, CCL2, CCL3, CCL3L1, CCL4 was analyzed using real-time RT-PCR after 6, 10 and 24 h of nickel sulphate exposure. In response to 100 μM nickel sulphate MUTZ-3 DC revealed slightly upregulated mRNA levels after 24 h, whereas 300 μM induced transcription of CCL3, CCL3L1 and IL8 significantly after 6 or 10 h. These cytokine data correspond to the previously observed effects of 100 μM nickel sulphate in CD34DC. Our findings underline the stimulatory capacity of nickel sulphate in MUTZ-3 DC with regard to cytokine mRNA induction, but not surface marker expression. Compared to CD34DC, however, the studied endpoint markers seemed to be less inducible, making the MUTZ-3 DC model in its presented form less suitable for in vitro testing of sensitization. Further assessment of MUTZ-3 DC using other differentiation protocols and an extended set of chemicals will be required to reveal whether this cell line may be a valid alternative model system to primary CD34DC. |
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Language
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English
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Source (journal)
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Toxicology in vitro. - Oxford
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Publication
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Oxford
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2009
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ISSN
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0887-2333
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DOI
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10.1016/J.TIV.2009.08.022
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Volume/pages
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23
:8
(2009)
, p. 1477-1481
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ISI
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000272276600007
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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