title: Tacrolimus modulates dendritic cell activation in the sensitization phase of allergic contact dermatitis.
abstract: 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.
authors.affiliation: Department of Dermatology and Allergology, RWTH Aachen University Hospital, Aachen, Germany. hagen.ott@post.rwth-aachen.de
authors.forename: H
authors.initials: H
authors.lastname: Ott
authors.forename: J M
authors.initials: JM
authors.lastname: Baron
authors.forename: R
authors.initials: R
authors.lastname: Heise
authors.forename: C
authors.initials: C
authors.lastname: Skazik
authors.forename: H F
authors.initials: HF
authors.lastname: Merk
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D016209:Interleukin-8; D000171:Acrolein; D014302:Trinitrobenzenesulfonic Acid; D001623:Betamethasone; C012843:cinnamaldehyde; D016559:Tacrolimus