PMID- 25975990
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20171116
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 90
IP  - 4
DP  - 2016 Apr
TI  - Unsaturated compounds induce up-regulation of CD86 on dendritic cells in the in 
      vitro sensitization assay LCSA.
PG  - 927-36
LID - 10.1007/s00204-015-1527-4 [doi]
AB  - Unsaturated compounds are known to cause false-positive reactions in the local 
      lymph node assay (LLNA) but not in the guinea pig maximization test. We have 
      tested a panel of substances (succinic acid, undecylenic acid, 1-octyn-3-ol, 
      fumaric acid, maleic acid, linoleic acid, oleic acid, alpha-linolenic acid, 
      squalene, and arachidonic acid) in the loose-fit coculture-based sensitization 
      assay (LCSA) to evaluate whether unspecific activation of dendritic cells is a 
      confounder for sensitization testing in vitro. Eight out of 10 tested substances 
      caused significant up-regulation of CD86 on dendritic cells cocultured with 
      keratinocytes and would have been classified as sensitizers; only succinic acid 
      was tested negative, and squalene had to be excluded from data analysis due to 
      poor solubility in cell culture medium. Based on human data, only undecylenic 
      acid can be considered a true sensitizer. The true sensitizing potential of 
      1-octyn-3-ol is uncertain. Fumaric acid and its isomer maleic acid are not known 
      as sensitizers, but their esters are contact allergens. A group of 18- to 
      20-carbon chain unsaturated fatty acids (linoleic acid, oleic acid, 
      alpha-linolenic acid, and arachidonic acid) elicited the strongest reaction in 
      vitro. This is possibly due to the formation of pro-inflammatory lipid mediators 
      in the cell culture causing nonspecific activation of dendritic cells. In 
      conclusion, both the LLNA and the LCSA seem to provide false-positive results for 
      unsaturated fatty acids. The inclusion of T cells in dendritic cell-based in 
      vitro sensitization assays may help to eliminate false-positive results due to 
      nonspecific dendritic cell activation. This would lead to more accurate 
      prediction of sensitizers, which is paramount for consumer health protection and 
      occupational safety.
FAU - Frohwein, Thomas Armin
AU  - Frohwein TA
AD  - Institute of Clinical Pharmacology and Toxicology, Charite - Universitatsmedizin 
      Berlin, Chariteplatz 1, 10117, Berlin, Germany.
FAU - Sonnenburg, Anna
AU  - Sonnenburg A
AD  - Institute of Clinical Pharmacology and Toxicology, Charite - Universitatsmedizin 
      Berlin, Chariteplatz 1, 10117, Berlin, Germany.
FAU - Zuberbier, Torsten
AU  - Zuberbier T
AD  - Department of Dermatology and Allergy, Charite - Universitatsmedizin Berlin, 
      Chariteplatz 1, 10117, Berlin, Germany.
FAU - Stahlmann, Ralf
AU  - Stahlmann R
AD  - Institute of Clinical Pharmacology and Toxicology, Charite - Universitatsmedizin 
      Berlin, Chariteplatz 1, 10117, Berlin, Germany.
FAU - Schreiner, Maximilian
AU  - Schreiner M
AD  - Institute of Clinical Pharmacology and Toxicology, Charite - Universitatsmedizin 
      Berlin, Chariteplatz 1, 10117, Berlin, Germany. dr.max.schreiner@gmail.com.
AD  - Department of Internal Medicine (Abt. I), Bundeswehrkrankenhaus Berlin, 
      Scharnhorststrasse 13, 10115, Berlin, Germany. dr.max.schreiner@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150516
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (B7-2 Antigen)
RN  - 0 (CD86 protein, human)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - AB6MNQ6J6L (Succinic Acid)
SB  - IM
MH  - Animals
MH  - B7-2 Antigen/*metabolism
MH  - Coculture Techniques/methods
MH  - Dendritic Cells/drug effects/immunology
MH  - False Positive Reactions
MH  - Fatty Acids, Unsaturated/*immunology/toxicity
MH  - Guinea Pigs
MH  - Humans
MH  - Keratinocytes/cytology/drug effects/immunology
MH  - Local Lymph Node Assay
MH  - Skin Tests/*methods
MH  - Succinic Acid/immunology/toxicity
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - Coculture
OT  - Dendritic cells
OT  - Keratinocytes
OT  - Regulative toxicology
OT  - Sensitization assay
EDAT- 2015/05/16 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/05/16 06:00
PHST- 2014/10/21 00:00 [received]
PHST- 2015/05/05 00:00 [accepted]
PHST- 2015/05/16 06:00 [entrez]
PHST- 2015/05/16 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 10.1007/s00204-015-1527-4 [pii]
AID - 10.1007/s00204-015-1527-4 [doi]
PST - ppublish
SO  - Arch Toxicol. 2016 Apr;90(4):927-36. doi: 10.1007/s00204-015-1527-4. Epub 2015 
      May 16.