Tacrolimus modulates dendritic cell activation in the sensitization phase of allergic contact dermatitis.
BACKGROUND
Knowledge of the effect of topically applied calcineurin antagonists such as tacrolimus on the sensitization phase of allergic contact dermatitis is currently limited.


OBJECTIVE
To investigate tacrolimus-dependent immunomodulation on gene expression alterations in human antigen-presenting cells which are stimulated with small-molecular-weight contact allergens.


METHODS
Monocyte-derived dendritic cells (moDC) and THP-1 cells were stimulated with the contact sensitizer cinnamic aldehyde (CAld) and compared with the very strong experimental sensitizer 2,4,6-trinitrobenzene sulfonic acid (TNBS) in vitro. Quantitative PCR analysis was used to detect gene expression changes, particularly of interleukin (IL) 8, as an indicator of differential dendritic cell (DC) gene expression after sensitizer stimulation in the absence or presence of tacrolimus and betamethasone at two different concentrations.


RESULTS
DC activation was clearly demonstrated by a significant IL-8 upregulation after 24 h, whereas tacrolimus or betamethasone alone did not affect IL-8 baseline expression. Betamethasone and, to a lesser extent, tacrolimus led to a marked reduction of chemical-induced IL-8 expression by TNBS and CAld.


CONCLUSIONS
The results of the present study support the hypothesis that the calcineurin inhibitor tacrolimus has modulatory effects on human antigen-presenting cells during the sensitization phase of allergic contact dermatitis. In addition, moDC as well as THP-1 cells may serve as a system to study immune-modulating effects of drugs such as glucocorticoids or calcineurin antagonists.
Ott
H
H
Department of Dermatology and Allergology, RWTH Aachen University Hospital, Aachen, Germany. hagen.ott@post.rwth-aachen.de
Baron
J M
JM
Heise
R
R
Skazik
C
C
Merk
H F
HF
D000171:Acrolein / Q000031:analogs & derivatives / Q000633:toxicity; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D001623:Betamethasone / Q000494:pharmacology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D016559:Tacrolimus / Q000494:pharmacology*; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D007166:Immunosuppressive Agents; D016209:Interleukin-8; D000171:Acrolein; D014302:Trinitrobenzenesulfonic Acid; D001623:Betamethasone; C012843:cinnamaldehyde; D016559:Tacrolimus