PMID- 23624239
OWN - NLM
STAT- MEDLINE
DCOM- 20140312
LR  - 20210702
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 27
IP  - 6
DP  - 2013 Sep
TI  - Evaluation of selected biomarkers for the detection of chemical sensitization in 
      human skin: a comparative study applying THP-1, MUTZ-3 and primary dendritic 
      cells in culture.
PG  - 1659-69
LID - S0887-2333(13)00096-9 [pii]
LID - 10.1016/j.tiv.2013.04.009 [doi]
AB  - Dendritic cells (DCs) exhibit the unique capacity to induce T cell 
      differentiation and proliferation, two processes that are crucially involved in 
      allergic reactions. By combining the exclusive potential of DCs as the only 
      professional antigen-presenting cells of the human body with the well known 
      handling advantages of cell lines, cell-based alternative methods aimed at 
      detecting chemical sensitization in vitro commonly apply DC-like cells derived 
      from myeloid cell lines. Here, we present the new biomarkers programmed 
      death-ligand 1 (PD-L1), DC immunoreceptor (DCIR), IL-16, and 
      neutrophil-activating protein-2 (NAP-2), all of which have been detectable in 
      primary human DCs upon exposure to chemical contact allergens. To evaluate the 
      applicability of DC-like cells in the prediction of a chemical's sensitization 
      potential, the expression of cell surface PD-L1 and DCIR was analyzed. In 
      contrast to primary DCs, only minor subpopulations of MUTZ-3 and THP-1 cells 
      presented PD-L1 or DCIR at their surface. After exposure to increasing 
      concentrations of nickel and cinnamic aldehyde, the expression level of PD-L1 and 
      DCIR revealed much stronger affected on monocyte-derived DCs (MoDCs) or 
      Langerhans cells (MoLCs) when compared to THP-1 and MUTZ-3 cells. Applying 
      protein profiler arrays we further identified the soluble factors NAP-2, IL-16, 
      IL-8 and MIP-1alpha as sensitive biomarkers showing the capacity to discriminate 
      sensitizing from non-sensitizing chemicals or irritants. An allergen-specific 
      release of IL-8 and MIP-1alpha could be detected in the supernatants of MoDCs and 
      MoLCs and also in MUTZ-3 and THP-1 cells, though at much lower levels. On the 
      protein and transcriptional level, NAP-2 and IL-16 indicated sensitizers most 
      sensitively and specifically in MoDCs. Altogether, we have proven the reciprocal 
      regulated surface molecules PD-L1 and DCIR and the soluble factors MIP-1alpha, NAP-2 
      and IL-16 as reliable biomarkers for chemical sensitization. We further show that 
      primary DCs are significantly different in their phenotype and function compared 
      to DC-like cell lines. Since they demonstrated higher absolute values and a 
      broader range in biomarker expression, we propose that MoDCs represent an optimal 
      and robust sensor test system well suited to identify and classify chemicals with 
      an allergic potential.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Hitzler, Manuel
AU  - Hitzler M
AD  - German Federal Institute for Risk Assessment (BfR), Department of Product Safety, 
      Berlin, Germany. Manuel.Hitzler@bfr.bund.de
FAU - Bergert, Antje
AU  - Bergert A
FAU - Luch, Andreas
AU  - Luch A
FAU - Peiser, Matthias
AU  - Peiser M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130426
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Allergens)
RN  - 0 (B7-2 Antigen)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Biomarkers)
RN  - 0 (CD274 protein, human)
RN  - 0 (CD86 protein, human)
RN  - 0 (CLEC4A protein, human)
RN  - 0 (Interleukin-16)
RN  - 0 (Interleukin-8)
RN  - 0 (Lectins, C-Type)
RN  - 0 (MAPKAP1 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (PPBP protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (beta-Thromboglobulin)
RN  - 3T8H1794QW (Eugenol)
RN  - 7864XYD3JJ (Acrolein)
RN  - 7OV03QG267 (Nickel)
RN  - SR60A3XG0F (cinnamaldehyde)
SB  - IM
MH  - Acrolein/analogs & derivatives/toxicity
MH  - Adaptor Proteins, Signal Transducing/genetics/metabolism
MH  - Allergens/*toxicity
MH  - B7-2 Antigen/metabolism
MH  - B7-H1 Antigen/metabolism
MH  - Biomarkers/metabolism
MH  - Cell Line
MH  - Cells, Cultured
MH  - Dendritic Cells/*drug effects/metabolism
MH  - Eugenol/toxicity
MH  - Humans
MH  - Interleukin-16/genetics/metabolism
MH  - Interleukin-8/genetics/metabolism
MH  - Langerhans Cells/*drug effects/metabolism
MH  - Lectins, C-Type/metabolism
MH  - Membrane Glycoproteins/metabolism
MH  - Nickel/toxicity
MH  - RNA, Messenger/metabolism
MH  - Receptors, Immunologic/metabolism
MH  - Skin Irritancy Tests
MH  - beta-Thromboglobulin/genetics/metabolism
OTO - NOTNLM
OT  - Biomarker
OT  - Contact allergy
OT  - DCIR
OT  - Dendritic cell
OT  - IL-16
OT  - MIP-1alpha
OT  - MUTZ-3
OT  - NAP-2
OT  - PD-L1
OT  - Sensitization assay
OT  - THP-1
EDAT- 2013/04/30 06:00
MHDA- 2014/03/13 06:00
CRDT- 2013/04/30 06:00
PHST- 2012/12/12 00:00 [received]
PHST- 2013/02/15 00:00 [revised]
PHST- 2013/04/11 00:00 [accepted]
PHST- 2013/04/30 06:00 [entrez]
PHST- 2013/04/30 06:00 [pubmed]
PHST- 2014/03/13 06:00 [medline]
AID - S0887-2333(13)00096-9 [pii]
AID - 10.1016/j.tiv.2013.04.009 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2013 Sep;27(6):1659-69. doi: 10.1016/j.tiv.2013.04.009. Epub 
      2013 Apr 26.