Corticosteroids but not pimecrolimus affect viability, maturation and immune function of murine epidermal Langerhans cells.
Given the importance of dendritic cells in the immune response, we investigated the effect of corticosteroids (CS) on the integrity, survival, and function of murine Langerhans cells (LC) in comparison with pimecrolimus, a novel anti-inflammatory drug for the topical treatment of atopic dermatitis. BALB/c mice were treated twice on one day with ethanolic solutions of the compounds. At 24-72 h after the last application, we observed fragmented DNA, caspase-3 activity, and an upregulation of CD95 expression in LC from mice treated with CS but not in LC of pimecrolimus- or vehicle-treated animals. CS-epidermal cell (EC) supernatants but not pimecrolimus-EC supernatants contained significantly lower amounts of soluble factors (GM-CSF, TNF-alpha, IL-1alpha) required for LC survival and maturation than EC supernatants from vehicle-treated mice. With regard to LC maturation, CS but not pimecrolimus inhibited the expression of CD25, CD205, and costimulatory molecules. In line with this, LC from pimecrolimus-treated mice were similar to LC from vehicle-treated mice in their capacity to stimulate antigen-presenting function and migration, whereas LC from CS-treated mice were greatly impaired in these abilities. In summary, our data show for the first time that CS but not pimecrolimus induce apoptosis in LC in situ, implying that the prolonged use of CS could have adverse effects on the skin immune system.
Hoetzenecker
Wolfram
W
DIAID, Department of Dermatology, Medical University of Vienna, Austria.
Meingassner
Josef G
JG
Ecker
Rupert
R
Stingl
Georg
G
Stuetz
Anton
A
Elbe-Bürger
Adelheid
A
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002990:Clobetasol / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D022061:Tacrolimus Binding Protein 1A / Q000032:analysis
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D002990:Clobetasol; D022061:Tacrolimus Binding Protein 1A; D006854:Hydrocortisone; D016559:Tacrolimus