المؤلفون: Alicja Krejner, Ulrich Mrowietz, Anika Bruhs, Agatha Schwarz, Thomas Schwarz, Ulrike Wehkamp

المصدر: Archives of Dermatological Research. 310:751-758

مصطلحات موضوعية: Keratinocytes, 0301 basic medicine, Anti-Inflammatory Agents, Receptors, Cell Surface, Stimulation, Inflammation, Dermatology, Pharmacology, Administration, Cutaneous, Receptors, G-Protein-Coupled, 03 medical and health sciences, chemistry.chemical_compound, Psoriatic skin, 0302 clinical medicine, Psoriasis, medicine, Humans, Receptor, Skin, G protein-coupled receptor, Sodium butyrate, General Medicine, medicine.disease, Up-Regulation, 030104 developmental biology, chemistry, Case-Control Studies, Butyric Acid, medicine.symptom, Ex vivo, 030215 immunology

الوصف: The G-protein-coupled receptors GPR43 and GPR109a are known to play an important role in mediating anti-inflammatory and anti-cancer functions in the gut. Short-chain fatty acids, such as sodium butyrate (SB), are activators of GPR43 and GPR109a and thereby promote anti-inflammatory effects. The present study aimed to examine the expression of these receptors and their reaction to SB in psoriasis. Lesional and non-lesional biopsies of 6 psoriasis patients and of 4 controls were obtained and stained for GPR109a and GPR43. Ex vivo stimulation with SB was performed on fresh biopsy material. Lesional and non-lesional psoriatic skin showed a decreased expression of GPR109a and GPR43 on keratinocytes in comparison with control skin. Topical application of SB was able to increase the low-level expression of both receptors. The data suggest that SB by restoring the impaired expression of GPR109a and GPR43 might exert anti-inflammatory effects and may be utilized as a topical tool for the treatment of psoriasis, which has to be proven in future clinical trials.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e30f087cb22f16f86a5d7192f511651Test
https://doi.org/10.1007/s00403-018-1865-1Test

المؤلفون: Christian Jantschitsch, Thomas Schwarz, Agatha Schwarz, Susanne Kimeswenger, David A. De Luca, Barbara Sterniczky, Dagmar Födinger

المصدر: Archives of Dermatological Research. 310:529-532

مصطلحات موضوعية: 0301 basic medicine, Ultraviolet Rays, Biopsy, Dermatology, Biology, Melanocyte, Mice, 03 medical and health sciences, MART-1 Antigen, Immune system, medicine, Animals, Humans, Melanoma, Ultraviolet radiation, integumentary system, Epidermis (botany), medicine.diagnostic_test, fungi, General Medicine, Hair follicle, medicine.disease, Molecular biology, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Epidermal Cells, Melanocytes, Female, Epidermis, Hair Follicle, Biomarkers

الوصف: Adult wild-type mice are not supposed to be proper models for ultraviolet radiation (UVR)-induced melanoma since melanocytes are confined to hair follicles and cannot be sufficiently reached by UVR. On the other hand, in mutated mouse models used for melanoma research limitations, including an altered immune system and selection of affected pathways, lead to tumors phenotypically quite different from naturally occurring melanomas. We compared the distribution of epidermal melanocytes in UVR and not-UVR-exposed wild-type C57BL/6 mice. Starting at the age of 8 weeks, mice were exposed to physiologic doses of UVR three times weekly over 16 weeks. Back skin biopsies were taken 4, 8, 12 and 16 weeks after initiation of exposure, and stained for Melan-A, representing a highly selective marker for melanocytes. Surprisingly, after exposure to UVR, Melan-A positive cells were detected also in the interfollicular epidermis of C57BL/6 mice. We conclude that UVR is capable of inducing interfollicular epidermal melanocytes in wild-type mice.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::696b42518308bcf6ab2eb8403d33c57aTest
https://doi.org/10.1007/s00403-018-1840-xTest

المؤلفون: Mana Kaveh, Melina Mescher, Thomas Haarmann-Stemmann, Siraz Shaik, Julia Tigges, Agatha Schwarz, Stephan Meller, Stephan Alexander Braun, Bernhard Homey, Jean Krutmann, Marius Pollet, Anika Bruhs, Katrin Frauenstein, Christoph F.A. Vogel, Thierry Douki, Kevin Sondenheimer, Charlotte Esser

المصدر: Cell Death Differ

مصطلحات موضوعية: Keratinocytes, Neoplasms, Radiation-Induced, Skin Neoplasms, DNA Repair, Ultraviolet Rays, Apoptosis, medicine.disease_cause, Cell Line, Mice, medicine, Animals, Humans, DNA Breaks, Double-Stranded, RNA, Small Interfering, Molecular Biology, Mice, Knockout, Mice, Hairless, business.industry, Correction, Cell Cycle Checkpoints, Cell Biology, Receptors, Aryl Hydrocarbon, Pyrimidine Dimers, Carcinoma, Squamous Cell, Cancer research, RNA Interference, Carcinogenesis, business, Cyclin-Dependent Kinase Inhibitor p27, Nucleotide excision repair

الوصف: Ultraviolet B (UVB) radiation induces mutagenic DNA photoproducts, in particular cyclobutane pyrimidine dimers (CPDs), in epidermal keratinocytes (KC). To prevent skin carcinogenesis, these DNA photoproducts must be removed by nucleotide excision repair (NER) or apoptosis. Here we report that the UVB-sensitive transcription factor aryl hydrocarbon receptor (AHR) attenuates the clearance of UVB-induced CPDs in human HaCaT KC and skin from SKH-1 hairless mice. Subsequent RNA interference and inhibitor studies in KC revealed that AHR specifically suppresses global genome but not transcription-coupled NER. In further experiments, we found that the accelerated repair of CPDs in AHR-compromised KC depended on a modulation of the p27 tumor suppressor protein. Accordingly, p27 protein levels were increased in AHR-silenced KC and skin biopsies from AHR

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ff3a643948e74ca5602720fd5cd250e4Test
https://doi.org/10.1038/s41418-019-0440-4Test

المؤلفون: Agatha Schwarz, Lesley E. Rhodes, Thomas Schwarz, Fatemeh Navid, Regine Gläser, Sarah Felton

المصدر: Photochemical & Photobiological Sciences. 12:29-36

مصطلحات موضوعية: Lupus erythematosus, Innate immune system, integumentary system, Ultraviolet Rays, Antimicrobial peptides, Human skin, Biology, medicine.disease, Acquired immune system, Dermatitis, Atopic, Up-Regulation, Immune system, Downregulation and upregulation, Immune System, Psoriasis, Rosacea, Immunology, medicine, Humans, Lupus Erythematosus, Systemic, Vitamin D, Physical and Theoretical Chemistry, Antimicrobial Cationic Peptides

الوصف: This article reviews recent data on the expression, regulation and activation of antimicrobial peptides (AMP) in human skin, and considers their potential protective and pro-inflammatory roles following upregulation by ultraviolet radiation (UVR). Antimicrobial peptides are small peptides that are key components of the innate immune system, originally identified by their vital role in protecting the body-environment interface from infection. However, it has now become clear that AMP have more extensive actions, including the provision of pivotal links with the adaptive immune system. Moreover, aberrant AMP expression may contribute to immuno-modulated inflammatory dermatoses including psoriasis, eczema and the photoaggravated condition lupus erythematosus. Recent work has demonstrated the direct upregulation of AMP in healthy skin by cutaneous UVR exposure. This may serve to protect the skin from risks imposed by both the biophysical barrier-compromise and the immunosuppression that are attributable to UVR exposure. Furthermore, it is observed that UVR provokes upregulation of AMP in an atypical manner in the photosensitivity disorder polymorphic light eruption. Dysregulated UVR responses of these pro-inflammatory proteins may play a role in the pathogenesis of certain immune-mediated diseases caused or aggravated by sunlight.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b0a45ddaf81d10cce8945133f5a1d28Test
https://doi.org/10.1039/c2pp25158bTest

المؤلفون: Dagmar Kulms, Birgit Pöppelmann, H Düssmann, Thomas Schwarz, Agatha Schwarz, Sonja Ständer

المصدر: Cell Death & Differentiation. 9:598-608

مصطلحات موضوعية: Cytochalasin B, Ultraviolet Rays, DNA damage, CASP8 and FADD-Like Apoptosis Regulating Protein, Apoptosis, Cytochrome c Group, Biology, Caspase 8, Humans, fas Receptor, FADD, Cytoskeleton, Molecular Biology, Caspase 3, Intracellular Signaling Peptides and Proteins, Cell Biology, Fas receptor, Actin cytoskeleton, Caspase Inhibitors, Molecular biology, Actins, Caspase 9, Cell biology, Caspases, biology.protein, Receptor clustering, biological phenomena, cell phenomena, and immunity, Carrier Proteins, BH3 Interacting Domain Death Agonist Protein, DNA Damage, HeLa Cells

الوصف: Activation of the death receptor CD95 by its ligand or by UV radiation is associated with receptor clustering. The mechanism underlying this clustering is mostly unclear. Here we show that although disruption of the actin cytoskeleton by cytochalasin B (CyB) itself induces moderate apoptosis, it enhances apoptosis in HeLa cells induced either by UV radiation or an agonistic anti-CD95 antibody. CyB augments UV-induced apoptosis independently of UV-mediated DNA damage, since induction of DNA repair by exogenous DNA repair enzymes did not alter its enhancing effect. Inhibition of caspase-8, the most upstream caspase in CD95 signaling, blocked the apoptotic effect of CyB and the enhancing effect on UV- and CD95-induced apoptosis. Confocal laser scanning microscopy revealed that (i) CyB induces CD95 clustering, (ii) enhances UV-induced CD95 clustering, and (iii) CD95 clusters colocalize with disrupted actin filaments, suggesting a link between receptor clustering and actin rearrangement. Disruption of CD95 signaling by a dominant negative mutant of the signaling protein FADD protected from CyB-induced apoptosis and prevented the UV-enhancing effect. Accordingly, both the apoptotic and the enhancing effect of CyB was reduced in epidermal cells obtained from CD95 deficient mice (lpr) when compared to wild-type mice. These data suggest that disruption of the cytoskeleton causes apoptosis via activation of CD95 and enhances UV-induced apoptosis, possibly via aiding receptor clustering.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e286cd03c2e8072e5c536cd031fdbf20Test
https://doi.org/10.1038/sj.cdd.4401002Test