Christoph M Schempp

Universitätsklinikum Freiburg, Freiburg an der Elbe, Lower Saxony, Germany

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Publications (111)284.56 Total impact

  • Ute Wölfle · Birgit Haarhaus · Christoph M. Schempp ·
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    ABSTRACT: Keratinocytes express the bitter taste receptors TAS2R1 and TAS2R38. Amarogentin as an agonist for TAS2R1 and other TAS2Rs promotes keratinocyte differentiation. Similarly, mast cells are known to express bitter taste receptors. The aim of this study was to assess whether bitter compounds display immunomodulatory effects on these immunocompetent cells in the skin, so that they might be a target in chronic inflammatory diseases such as atopic dermatitis and psoriasis. Here, we investigated the impact of amarogentin on substance P-induced release of histamine and TNF- α from the human mast cell line LAD-2. Furthermore, the effect of amarogentin on HaCaT keratinocytes costimulated with TNF- α and histamine was investigated. Amarogentin inhibited in LAD-2 cells substance P-induced production of newly synthesized TNF- α , but the degranulation and release of stored histamine were not affected. In HaCaT keratinocytes histamine and TNF- α induced IL-8 and MMP-1 expression was reduced by amarogentin to a similar extent as with azelastine. In conclusion amarogentin displays immunomodulatory effects in the skin by interacting with mast cells and keratinocytes.
    Mediators of Inflammation 11/2015; 2015(1-2):1-8. DOI:10.1155/2015/630128 · 3.24 Impact Factor
  • Ute Wölfle · Birgit Haarhaus · Astrid Kersten · Bernd Fiebich · Martin J Hug · Christoph M Schempp ·
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    ABSTRACT: Salicin from willow bark has been used throughout centuries in China and Europe for the treatment of pain, headache, and inflammatory conditions. Recently, it could be demonstrated that salicin binds and activates the bitter taste receptor TAS2R16. Studies on rodent tissues showed the general expression of bitter taste receptors (TAS2Rs) in rodent brain. Here, we demonstrate the expression of hTAS2R16 in human neuronal tissues and the neuroblastoma cell line SH-SY5Y. The functionality was analyzed in the neuroblastoma cell line SH-SY5Y after stimulation with salicin, a known TAS2R16 agonist. In this setting salicin induced in SH-SY5Y cells phosphorylation of ERK and CREB, the key transcription factor of neuronal differentiation. PD98059, an inhibitor of the ERK pathway, as well as probenecid, a TAS2R16 antagonist, inhibited receptor phosphorylation as well as neurite outgrowth. These data show that salicin might modulate neurite outgrowth by bitter taste receptor activation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Phytotherapy Research 06/2015; 29(10). DOI:10.1002/ptr.5400 · 2.66 Impact Factor
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    ABSTRACT: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease that affects both children and adults in an increasing manner. The treatment of AD often reduces subjective skin parameters, such as itching, dryness, and tension, but the inflammation cannot be cured. Laser scanning microscopy was used to investigate the skin surface, epidermal, and dermal characteristics of dry and atopic skin before and after treatment with an ointment rich in hyperforin, which is known for its anti-inflammatory effects. The results were compared to subjective parameters and transepidermal water loss, stratum corneum moisture, and stratum corneum lipids. Using biophysical methods, in particular laser scanning microscopy, it was found that atopic skin has distinct features compared to healthy skin. Treatment with a hyperforin-rich ointment resulted in an improvement of the stratum corneum moisture, skin surface dryness, skin lipids, and the subjective skin parameters, indicating that the barrier is stabilized and improved by the ointment. But in contrast to the improved skin surface, the inflammation in the deeper epidermis/dermis often continues to exist. This could be clearly shown by the reflectance confocal microscopy (RCM) measurements. Therefore, RCM measurements could be used to investigate the progress in treatment of atopic dermatitis.
    Journal of Biomedical Optics 05/2015; 20(5):51013. DOI:10.1117/1.JBO.20.5.051013 · 2.86 Impact Factor
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    ABSTRACT: Recent studies have shown that human bitter taste receptors (TAS2Rs) are not only expressed in mucous epithelial cells of the tongue, but also in epithelial cells of the colon, stomach and upper respiratory tract. These cell types come in close contact with external bitter compounds by ingestion or breathing. In the present work we addressed the question whether bitter taste receptors might also be expressed in cornified epithelial cells of the skin. Here, we show for the first time the expression of TAS2R1 and TAS2R38 in human skin. Double staining of HaCaT cells and primary keratinocytes demonstrated the colocalization of TAS2R1 and TAS2R38 with the adaptor protein α-gustducin that is essential for signal transduction upon ligand binding. To test if TAS2Rs in keratinocytes are functional, we stimulated HaCaT cells with diphenidol, a clinically used bitter-tasting antiemetic, or amarogentin, the bitterest plant substance, that binds TAS2Rs, including TAS2R1 and TAS2R38. Diphenidol and amarogentin induced calcium influx. Furthermore, in keratinocytes diphenidol and amarogentin stimulated the expression of the differentiation markers keratin 10, involucrin and transglutaminase. Therefore, apart from the known role in mucous membranes of the gastrointestinal tract, TAS2Rs are expressed in the epidermis and might play a role in keratinocyte differentiation. © 2015 S. Karger AG, Basel.
    Planta Medica 01/2015; 28(3):137-146. DOI:10.1159/000367631 · 2.15 Impact Factor
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    ABSTRACT: No abstract is available for this article.
    Journal der Deutschen Dermatologischen Gesellschaft 12/2014; 12(12):1138-40. DOI:10.1111/ddg.12430 · 2.05 Impact Factor
  • S. Müller · C.M. Schempp · T. Jakob ·

    Journal of the European Academy of Dermatology and Venereology 12/2014; DOI:10.1111/jdv.12922 · 2.83 Impact Factor

  • Journal der Deutschen Dermatologischen Gesellschaft 12/2014; 12(12). DOI:10.1111/ddg.12430_suppl · 2.05 Impact Factor

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    ABSTRACT: Reactive oxygen and nitrogen species (ROS/RNS) which may exist as radicals or nonradicals, as well as reactive sulfur species and reactive carbon species, play a major role in aging processes and in carcinogenesis. These reactive molecule species (RMS), often referred to as 'free radicals' or oxidants, are partly by-products of the physiological metabolism. When RMS concentrations exceed a certain threshold, cell compartments and cells are injured and destroyed. Endogenous physiological mechanisms are able to neutralize RMS to some extent, thereby limiting damage. In the skin, however, pollutants and particularly UV irradiation are able to produce additional oxidants which overload the endogenous protection system and cause early aging, debilitation of immune functions, and skin cancer. The application of antioxidants from various sources in skin care products and food supplements is therefore widespread, with increasingly effective formulations being introduced. The harmful effects of RMS (aside from impaired structure and function of DNA, proteins, and lipids) are: interference with specific regulatory mechanisms and signaling pathways in cell metabolism, resulting in chronic inflammation, weakening of immune functions, and degradation of tissue. Important control mechanisms are: MAP-kinases, the aryl-hydrocarbon receptor (AhR), the antagonistic transcription factors nuclear factor-κB and Nrf2 (nuclear factor erythroid 2-related factor 2), and, especially important, the induction of matrix metalloproteinases which degrade dermal connective tissue. Recent research, however, has revealed that RMS and in particular ROS/RNS are apparently also produced by specific enzyme reactions in an evolutionarily adapted manner. They may fulfill important physiologic functions such as the activation of specific signaling chains in the cell metabolism, defense against infectious pathogens, and regulation of the immune system. Normal physiological conditions are characterized by equilibrium of oxidative and antioxidative mechanisms. The application of antioxidants in the form of 'cosmeceuticals' or systemic 'nutraceuticals' should aim to support a physiologically balanced oxidation status in the skin. © 2014 S. Karger AG, Basel.
    Skin pharmacology and physiology 06/2014; 27(6):316-332. DOI:10.1159/000360092 · 2.37 Impact Factor
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    Ute Wölfle · Günter Seelinger · Christoph M Schempp ·
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    ABSTRACT: St. John's wort (Hypericum perforatum) has been intensively investigated for its antidepressive activity, but dermatological applications also have a long tradition. Topical St. John's wort preparations such as oils or tinctures are used for the treatment of minor wounds and burns, sunburns, abrasions, bruises, contusions, ulcers, myalgia, and many others. Pharmacological research supports the use in these fields. Of the constituents, naphthodianthrones (e.g., hypericin) and phloroglucinols (e.g., hyperforin) have interesting pharmacological profiles, including antioxidant, anti-inflammatory, anticancer, and antimicrobial activities. In addition, hyperforin stimulates growth and differentiation of keratinocytes, and hypericin is a photosensitizer which can be used for selective treatment of nonmelanoma skin cancer. However, clinical research in this field is still scarce. Recently, sporadic trials have been conducted in wound healing, atopic dermatitis, psoriasis, and herpes simplex infections, partly with purified single constituents and modern dermatological formulations. St. John's wort also has a potential for use in medical skin care. Composition and stability of pharmaceutical formulations vary greatly depending on origin of the plant material, production method, lipophilicity of solvents, and storage conditions, and this must be regarded with respect to practical as well as scientific purposes.
    Planta Medica 11/2013; 80(2). DOI:10.1055/s-0033-1351019 · 2.15 Impact Factor
  • Ute Wölfle · Birgit Haarhaus · Christoph M Schempp ·
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    ABSTRACT: Ultraviolet radiation induces DNA damage and oxidative stress which can result in skin inflammation, photoaging, and photocarcinogenesis. The flavonoid luteolin that is present in high amounts in the dyers weld, Reseda luteola, is one of the most potent antioxidative plant metabolites and also has ultraviolet-absorbing properties.The aim of this study was to determine whether tocopherol and ubiquinone add synergistic antioxidative values to luteolin. None of the substances showed cytotoxic effects in concentrations from 0.25 to 4 µg/mL. The photoprotective and antioxidant effect of equivalent concentrations of luteolin, tocopherol, and ubiquinone and their combination in a ratio of 4 : 4 : 1 were studied in solar simulator irradiated human skin fibroblasts. Luteolin had a half-maximal radical scavenging concentration of 2 µg/mL, whereas tocopherol and ubiquinone were only effective at higher concentrations. None of the substances showed a phototoxic effect, and only luteolin had a moderate photoprotective effect at 2 µg/mL. The combination of luteolin, tocopherol, and ubiquinone exerted a synergistic radical scavenging effect already at a concentration of 0.25 µg/mL and a complete photoprotection at 2 µg/mL.In summary, our findings suggest that the potent antioxidant and photoprotective effect of flavonoids like luteolin may be further increased by the addition of low concentrations of other antioxidants such as tocopherol and ubiquinone.
    Planta Medica 07/2013; 79(11). DOI:10.1055/s-0032-1328716 · 2.15 Impact Factor
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    ABSTRACT: Mistletoe extracts are often used in complementary cancer therapy although the efficacy of that therapy is controversially discussed. Approved mistletoe extracts contain mainly water soluble compounds of the mistletoe plant, i.e. mistletoe lectins. However, mistletoe also contains water-insoluble triterpenoids (mainly oleanolic acid) that have anti-tumorigenic effects. To overcome their loss in watery extracts we have solubilized mistletoe triterpenoids with cyclodextrins, thus making them available for in vivo cancer experiments. B16.F10 subcutaneous melanoma bearing C57BL/6 mice were treated with new mistletoe extracts containing both water soluble compounds and solubilized triterpenoids. Tumor growth and survival was monitored. In addition, histological examinations of the tumor material and tumor surrounding tissue were performed. Addition of solubilized triterpenoids increased the anti-tumor effects of the mistletoe extracts, resulting in reduced tumor growth and prolonged survival of the mice. Histological examination of the treated tumors showed mainly tumor necrosis and some apoptotic cells with active caspase-3 and TUNEL staining. A significant decrease of CD31-positive tumor blood vessels was observed after treatment with solubilized triterpenoids and different mistletoe extracts. We conclude that the addition of solubilized mistletoe triterpenoids to conventional mistletoe extracts improves the efficacy of mistletoe treatment and may represent a novel treatment option for malignant melanoma.
    PLoS ONE 04/2013; 8(4):e62168. DOI:10.1371/journal.pone.0062168 · 3.23 Impact Factor
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    ABSTRACT: Abstract Human skin is continuously exposed to solar radiation, which can result in photoaging, a process involving both dermal and, to a lesser extent, epidermal structures. Previously, we have shown that the flavonoid luteolin protects the epidermis from ultraviolet (UV)-induced damage by a combination of UV-absorbing, antioxidant, and antiinflammatory properties. The aim of the present study was to determine direct and indirect effects of luteolin on dermal fibroblasts as major targets of photoaging. Stimulation of fibroblasts with UVA light or the proinflammatory cytokine interleukin-20 (IL-20) is associated with wrinkled skin, increased IL-6 secretion, matrix metalloproteinase (MMP-1) expression, and hyaluronidase activity. All of these targets were inhibited by luteolin via interference with the p38 mitogen-activated protein kinase (MAPK) pathway. Next, we assessed the role of conditioned supernatants from keratinocytes irradiated with solar-simulated radiation (SSR) on nonirradiated dermal fibroblasts. In keratinocytes, luteolin inhibited SSR-induced production of IL-20, also via interference with the p38 MAPK pathway. Similarly, keratinocyte supernatant-induced IL-6 and MMP-1 expression in fibroblasts was reduced by pretreatment of keratinocytes with luteolin. Finally, these results were confirmed ex vivo on skin explants treated with luteolin before UV irradiation. Our results suggest that SSR-mediated production of soluble factors in keratinocytes is modulated by luteolin and may attenuate photoaging in dermal fibroblasts.
    Rejuvenation Research 10/2012; 15(5):466-475. DOI:10.1089/rej.2011.1309 · 3.31 Impact Factor
  • Peter Wolf · Dimitrios Georgas · Nordwig S Tomi · Christoph M Schempp · Klaus Hoffmann ·
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    ABSTRACT: Background: Previous work has indicated that extracorporeal photochemotherapy (ECP) may be a safe and effective treatment in patients with severe atopic dermatitis. Methods: We performed a prospective study to investigate the effect of a defined 20-week ECP protocol in patients with severe, refractory atopic dermatitis. The patient inclusion criteria included (i) disease duration of at least 1 year, (ii) SCORAD > 45, and (iii) resistance to first-line therapy, including topical steroids, topical calcineurin inhibitors, and one form of phototherapy (UVA, UVB, or PUVA) or one second-line therapy, including systemic steroids or cyclosporine. Ten patients (4 women and 6 men; age range 29 to 61 years) were enrolled and treated with two sessions of standard ECP in 2-week intervals for 12 weeks and 4-week intervals thereafter until week 20. The patients' clinical status and response was determined by SCORAD at baseline and every 2 weeks, and quality of life was assessed every 4 weeks using SKINDEX, SF-36, and FACT scores. Results: There was a statistically significant (p = 0.015) reduction of the mean SCORAD by 10.3 (95% CI, 2.5 to 18.0) from 64.8 at baseline to 54.5 (i.e., 15.9% reduction) at week 20. In a subset of patients (all of female sex), the relative reduction in SCORAD after ECP was more than 25% at week 20. Improvement in quality of life measured by SKINDEX, SF-36, and FACT did not reach statistical significance. Conclusions: We detected a small but significant therapeutic effect of ECP in patients with severe, refractory atopic dermatitis.
    Photochemical and Photobiological Sciences 09/2012; 12(1). DOI:10.1039/c2pp25203a · 2.27 Impact Factor
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    ABSTRACT: Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T cell-mediated skin disease induced by protein-reactive organic and inorganic chemicals. A key feature of contact allergens is their ability to trigger an innate immune response that leads to skin inflammation. Previous evidence from the mouse contact hypersensitivity (CHS) model suggests a role for endogenous activators of innate immune signaling. Here, we analyzed the role of contact sensitizer induced ROS production and concomitant changes in hyaluronic acid metabolism on CHS responses. We analyzed in vitro and in vivo ROS production using fluorescent ROS detection reagents. HA fragmentation was determined by gel electrophoresis. The influence of blocking ROS production and HA degradation by antioxidants, hyaluronidase-inhibitor or p38 MAPK inhibitor was analyzed in the murine CHS model. Here, we demonstrate that organic contact sensitizers induce production of reactive oxygen species (ROS) and a concomitant breakdown of the extracellular matrix (ECM) component hyaluronic acid (HA) to pro-inflammatory low molecular weight fragments in the skin. Importantly, inhibition of either ROS-mediated or enzymatic HA breakdown prevents sensitization as well as elicitation of CHS. These data identify an indirect mechanism of contact sensitizer induced innate inflammatory signaling involving the breakdown of the ECM and generation of endogenous danger signals. Our findings suggest a beneficial role for anti-oxidants and hyaluronidase inhibitors in prevention and treatment of ACD.
    PLoS ONE 07/2012; 7(7):e41340. DOI:10.1371/journal.pone.0041340 · 3.23 Impact Factor
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    ABSTRACT: Background. There is increasing evidence that reactive oxygen species play an important role in the development of both irritant and allergic contact dermatitis. Objectives. To assess the potential of topical antioxidants to prevent the development of experimentally induced irritant contact dermatitis. Methods. We evaluated the effect of a cream containing a combination of antioxidants on sodium lauryl sulfate-induced irritant contact dermatitis in the repetitive washing test. As readout parameters for skin barrier function and cutaneous inflammation stratum corneum hydration, cutaneous blood flow and transepidermal water loss were assessed in 25 volunteers with bioengineering methods. Results. In comparison with the cream base and a frequently used barrier cream, the antioxidant cream had high radical scavenging activity and effectively protected the skin from chemical-induced irritation. Conclusions. The superiority of the cream with antioxidants to the cream base suggests that reactive oxygen species, at least in part, play a role in the development of irritant contact dermatitis.
    Contact Dermatitis 05/2012; 67(4):234-237. DOI:10.1111/j.1600-0536.2012.02114.x · 3.75 Impact Factor
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    ABSTRACT: Hyperforin, a major constituent of St. John's Wort (Hypericum perforatum, HP), provides anti-inflammatory, anti-tumor, and anti-bacterial properties. Previous studies have shown anti-oxidative properties of St. John's Wort extracts; however, its free radical scavenging activity in skin cells or skin has not been assessed in detail so far. Therefore, the free radical scavenging activity of hyperforin was tested in the H(2)DCFDA-assay in vitro in HaCaT keratinocytes irradiated with solar simulated radiation. Hyperforin (EC(50) 0.7 μM corresponding to 0.42 μg/ml) was much more effective compared to Trolox (EC(50) 12 μg/ml) and N-acetylcysteine (EC(50) 847 μg/ml) without showing phototoxicity. The radical protection factor of a cream containing 1.5%w/w of a hyperforin-rich HP extract was determined to be 200 × 10(14) radicals/mg, indicating a high radical scavenging activity. The cream was further applied ex vivo on porcine ear skin and significantly reduced radical formation after infrared irradiation. Finally, the UV-protective effect of the HP cream was tested on 20 volunteers in a randomized, double-blind, vehicle-controlled study. HP cream significantly reduced UVB-induced erythema as opposed to the vehicle. Occlusive application of HP cream on non-irradiated test sites did not cause any skin irritation. Taken together, these results demonstrate that hyperforin is a powerful free radical scavenger.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 03/2012; 81(2):346-50. DOI:10.1016/j.ejpb.2012.03.002 · 3.38 Impact Factor

  • 39th Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung; 03/2012
  • P. R. Esser · U. Woelfle · T. Jakob · C. M. Schempp · S. F. Martin ·

    39th Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung; 03/2012
  • C M Strüh · S Jäger · C M Schempp · A Scheffler · S F Martin ·
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    ABSTRACT: The European mistletoe Viscum album L. is a plant used for remedies in cancer treatment. The benefit of commonly used aqueous extracts is controversial but the plant contains water insoluble triterpene acids providing interesting anticancer properties. Triterpene extracts (TE) from plants and single triterpenoids such as oleanolic acid (OA) or betulinic acid (BA) are known for their cytotoxic effects on cancer cell lines in vitro. We report here cytotoxic effects of a novel OA-rich triterpene extract from mistletoe (V. album L., Santalaceae) solubilized by 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) on B16.F10 mouse melanoma cells. The 2-HP-β-CD solubilized triterpene extract (STE) was highly cytotoxic by causing DNA fragmentation, followed by loss of membrane integrity and intracellular adenosine-5'-triphosphate (ATP). Blocking the caspase machinery by inhibitors aborted DNA fragmentation and delayed the cytotoxic effects but did not prevent cell death. The solubilization by 2-HP-β-CD allows a solvent-free application of triterpene extracts in the in vitro setting. These findings suggest the use of STE from mistletoe as a solvent-free anticancer drug for preclinical animal experiments and clinical trials. Copyright © 2012 John Wiley & Sons, Ltd.
    Phytotherapy Research 02/2012; 26(10):1507-12. DOI:10.1002/ptr.4604 · 2.66 Impact Factor

Publication Stats

2k Citations
284.56 Total Impact Points


  • 1996-2015
    • Universitätsklinikum Freiburg
      • Department of Dermatology and Venereology
      Freiburg an der Elbe, Lower Saxony, Germany
  • 1996-2014
    • University of Freiburg
      • Department of Pathology
      Freiburg, Baden-Württemberg, Germany
  • 1997-2006
    • Universitäts-Herzzentrum Freiburg - Bad Krozingen
      باد کروزینگن, Baden-Württemberg, Germany