THP-1 monocytes but not macrophages as a potential alternative for CD34(+) dendritic cells to identify chemical skin sensitizers

Lambrechts, N; Verstraelen, S; Lodewyckx, H; Felicio, Ana; Hooyberghs, Jef; Witters, H; Van Tendeloo, V; Van Cauwenberge, P; Nelissen, I; Van Den Heuvel, R; Schoeters, G

HERO ID

1801129

Reference Type

Journal Article

Year

2009

Language

English

PMID

19371601

HERO ID 1801129
In Press No
Year 2009
Title THP-1 monocytes but not macrophages as a potential alternative for CD34(+) dendritic cells to identify chemical skin sensitizers
Authors Lambrechts, N; Verstraelen, S; Lodewyckx, H; Felicio, Ana; Hooyberghs, Jef; Witters, H; Van Tendeloo, V; Van Cauwenberge, P; Nelissen, I; Van Den Heuvel, R; Schoeters, G
Journal Toxicology and Applied Pharmacology
Volume 236
Issue 2
Page Numbers 221-230
Abstract Early detection of the sensitizing potential of chemicals is an emerging issue for chemical, pharmaceutical and cosmetic industries. In our institute, an in vitro classification model for prediction of chemical-induced skin sensitization based on gene expression signatures in human CD34+ progenitor-derived dendritic cells (DC) has been developed. This primary cell model is able to closely mimic the induction phase of sensitization by Langerhans cells in the skin, but it has drawbacks, such as the availability of cord blood. The aim of this study was to investigate whether human in vitro cultured THP-1 monocytes or macrophages display a similar expression profile for 13 predictive gene markers previously identified in DC and whether they also possess a discriminating capacity towards skin sensitizers and non-sensitizers based on these marker genes. To this end, the cell models were exposed to 5 skin sensitizers (ammonium hexachloroplatinate IV, 1-chloro-2,4-dinitrobenzene, eugenol, para-phenylenediamine, and tetramethylthiuram disulfide) and 5 non-sensitizers (l-glutamic acid, methyl salicylate, sodium dodecyl sulfate, tributyltin chloride, and zinc sulfate) for 6, 10, and 24 h, and mRNA expression of the 13 genes was analyzed using real-time RT-PCR. The transcriptional response of 7 out of 13 genes in THP-1 monocytes was significantly correlated with DC, whereas only 2 out of 13 genes in THP-1 macrophages. After a cross-validation of a discriminant analysis of the gene expression profiles in the THP-1 monocytes, this cell model demonstrated to also have a capacity to distinguish skin sensitizers from non-sensitizers. However, the DC model was superior to the monocyte model for discrimination of (non-)sensitizing chemicals.
Doi 10.1016/j.taap.2009.01.026
Pmid 19371601
Wosid WOS:000264954300009
Is Certified Translation No
Dupe Override No
Comments Source: Web of Science WOS:000264954300009Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-62549136913&doi=10.1016%2fj.taap.2009.01.026&partnerID=40&md5=37a75963c33759bb0afab818c29c7cf5
Is Public Yes
Language Text English
Keyword Skin sensitization; in vitro sensitization testing; CD34(+) progenitor-derived dendritic cells; THP-1 monocytes; THP-1 macrophages