Anti-inflammatory and immune-regulatory mechanisms prevent contact hypersensitivity to Arnica montana L.
Christian Lass
Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany
Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg, Germany
Search for more papers by this authorMarc Vocanson
University Lyon 1, UFR Lyon-Sud, INSERM U851-IFR 128, CH Lyon-Sud, Lyon, France
Search for more papers by this authorSteffen Wagner
Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg, Germany
Search for more papers by this authorChristoph M. Schempp
Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany
Search for more papers by this authorJean-Francois Nicolas
University Lyon 1, UFR Lyon-Sud, INSERM U851-IFR 128, CH Lyon-Sud, Lyon, France
Search for more papers by this authorIrmgard Merfort
Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg, Germany
Search for more papers by this authorStefan F. Martin
Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany
Search for more papers by this authorChristian Lass
Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany
Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg, Germany
Search for more papers by this authorMarc Vocanson
University Lyon 1, UFR Lyon-Sud, INSERM U851-IFR 128, CH Lyon-Sud, Lyon, France
Search for more papers by this authorSteffen Wagner
Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg, Germany
Search for more papers by this authorChristoph M. Schempp
Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany
Search for more papers by this authorJean-Francois Nicolas
University Lyon 1, UFR Lyon-Sud, INSERM U851-IFR 128, CH Lyon-Sud, Lyon, France
Search for more papers by this authorIrmgard Merfort
Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg, Germany
Search for more papers by this authorStefan F. Martin
Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany
Search for more papers by this authorAbstract
Abstract: Sesquiterpene lactones (SL), secondary plant metabolites from flowerheads of Arnica, exert anti-inflammatory effects mainly by preventing nuclear factor (NF)-κB activation because of alkylation of the p65 subunit. Despite its known immunosuppressive action, Arnica has been classified as a plant with strong potency to induce allergic contact dermatitis. Here we examined the dual role of SL as anti-inflammatory compounds and contact allergens in vitro and in vivo. We tested the anti-inflammatory and allergenic potential of SL in the mouse contact hypersensitivity model. We also used dendritic cells to study the activation of NF-κB and the secretion of interleukin (IL)-12 in the presence of different doses of SL in vitro. Arnica tinctures and SL potently suppressed NF-κB activation and IL-12 production in dendritic cells at high concentrations, but had immunostimulatory effects at low concentrations. Contact hypersensitivity could not be induced in the mouse model, even when Arnica tinctures or SL were applied undiluted to inflamed skin. In contrast, Arnica tinctures suppressed contact hypersensitivity to the strong contact sensitizer trinitrochlorobenzene and activation of dendritic cells. However, contact hypersensitivity to Arnica tincture could be induced in acutely CD4-depleted MHC II knockout mice. These results suggest that induction of contact hypersensitivity by Arnica is prevented by its anti-inflammatory effect and immunosuppression as a result of immune regulation in immunocompetent mice.
Supporting Information
Figure S1. GC-chromatogram (total ionen current) of “Central European” Arnica tincture. The zoomed intervall contains the sesquiterpene lactones as labelled.
Figure S2. GC-chromatogramm (total ionen current) of “Spanish” Arnica tincture. The zoomed intervall contains the sesquiterpene lactones as labelled. Signals of dihydrohelenalin derivates show a double peak due to an intramolecular conversion in the injector.
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