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Charlotta Enerbäck - One of the best experts on this subject based on the ideXlab platform.
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overexpression of psoriasin s100a7 contributes to dysregulated differentiation in Psoriasis
Acta Dermato-venereologica, 2017Co-Authors: Annakarin Ekman, Jenny Vegfors, Cecilia Bivik Eding, Charlotta EnerbäckAbstract:Psoriasin, which is highly expressed in Psoriasis, is encoded by a gene located within the epidermal differentiation complex. The aim of this study was to investigate the effect of endogenous psori ...
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psoriasin s100a7 promotes stress induced angiogenesis
British Journal of Dermatology, 2016Co-Authors: Jenny Vegfors, Annakarin Ekman, Stefan W Stoll, Bivik C Eding, Charlotta EnerbäckAbstract:SummaryBackground Vascular modifications occur early in the development of Psoriasis, and angiogenesis is one of the key features in the pathogenesis of the disease. Objectives To identify the role of the S100 protein psoriasin in Psoriasis-associated angiogenesis. Methods The role of psoriasin in mediating angiogenesis was investigated by silencing psoriasin with small interfering RNA (siRNA) and measuring Psoriasis-associated angiogenic factors in human epidermal keratinocytes. The secretion of psoriasin and the effect of psoriasin on general regulators of angiogenesis in keratinocytes, and on endothelial cell migration, proliferation, tube formation and production of angiogenic mediators, was evaluated. Results Reactive oxygen species (ROS) and hypoxia induced the expression of psoriasin. Downregulation of psoriasin in keratinocytes using siRNA altered the ROS-induced expression of the Psoriasis-associated angiogenic factors vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor-like growth factor, matrix metalloproteinase 1 and thrombospondin 1. Overexpression of psoriasin altered several regulators of angiogenesis and led to the secretion of psoriasin. Treatment with extracellular psoriasin induced proliferation, migration and tube formation in dermal-derived endothelial cells to a similar extent as VEGF and interleukin-17, and induced the expression and release of proangiogenic mediators. These effects were suggested to be mediated by the PI3K and nuclear factor kappa B pathways. Conclusions These findings suggest that psoriasin expression is promoted by oxidative stress in keratinocytes and amplifies the ROS-induced expression of angiogenic factors relevant to Psoriasis. Moreover, extracellularly secreted psoriasin may act on dermal endothelial cells to contribute to key features angiogenesis.
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the expression of psoriasin s100a7 and cd24 is linked and related to the differentiation of mammary epithelial cells
PLOS ONE, 2012Co-Authors: Jenny Vegfors, Stina Petersson, Kornelia Polyak, Aniko Kovacs, Charlotta EnerbäckAbstract:Psoriasin (S100A7), a member of the S100 family of calcium-binding proteins, is highly expressed in high-grade ductal carcinoma in situ (DCIS) and in the benign hyperproliferative skin disorder Psoriasis. The gene that encodes psoriasin and many other S100 genes are located within a gene cluster on chromosome region 1q21, known as the epidermal differentiation complex. This cluster contains genes for several differentiation markers that play important roles in the terminal differentiation of the epidermis. The purpose of the present study was to evaluate the role of psoriasin in the differentiation process of mammary epithelial cells. Normal mammary epithelial cells (MCF10A) cultured in confluence and suspension, conditions known to induce psoriasin expression, demonstrated a shift towards a more differentiated phenotype indicated by an increase in the expression of the luminal differentiation markers CD24 and MUC1 and the reduced expression of the breast stem cell marker CD44. The expression of psoriasin and MUC1 was most pronounced in the CD24+-enriched fraction of confluent MCF10A cells. The shift towards a more differentiated phenotype was abolished upon the downregulation of psoriasin using short hairpin RNA (shRNA) and small interfering RNA (siRNA). Using specific inhibitors, we showed that psoriasin and CD24 expression was regulated by reactive oxygen species (ROS) and the nuclear factor (NF)-κB signaling pathways. While immunohistochemical analyses of DCIS showed heterogeneity, the expression of psoriasin and CD24 showed a similar staining pattern. Our findings suggest that the expression of psoriasin is linked to the luminal differentiation marker CD24 in mammary epithelial cells. Psoriasin demonstrated an essential role in the shift towards a more differentiated CD24+ phenotype, supporting the hypothesis that psoriasin plays a role in the differentiation of luminal mammary epithelial cells.
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psoriasin s100a7 increases the expression of ros and vegf and acts through rage to promote endothelial cell proliferation
Breast Cancer Research and Treatment, 2012Co-Authors: Emman Shubbar, Stina Petersson, Jenny Vegfors, Maria Carlstrom, Charlotta EnerbäckAbstract:Psoriasin (S100A7), originally identified in Psoriasis, is a calcium-binding protein belonging to the multigenic S100 family. In high-grade ductal carcinoma in situ, psoriasin was identified as one of the most abundant transcripts. We have previously shown that psoriasin was induced by reactive oxygen species (ROS). Moreover, the downregulation of psoriasin by short hairpin RNA (shRNA) led to the reduced expression of vascular endothelial growth factor (VEGF) and inhibited tumor growth in vivo. The aim of the present study was to investigate whether psoriasin could have direct effects on endothelial cells. In this study we demonstrated that psoriasin increased VEGF expression in mammary epithelial cells. The treatment of endothelial cells with recombinant psoriasin increased proliferation comparable to that of recombinant VEGF protein. No change in proliferation was seen when endothelial cells were infected with psoriasin-expressing adenoviruses, suggesting that the proliferative effect of psoriasin was mediated by a specific receptor. Treatment with sRAGE, targeting the receptor for advanced glycation end products (RAGE), thus inhibited endothelial cell proliferation and tube formation enhanced by recombinant psoriasin. We showed that VEGF expression was not induced by hydrogen peroxide, when psoriasin was silenced by shRNA, which led to the hypothesis that psoriasin induces ROS. Indeed, psoriasin was shown to induce ROS in both endothelial and epithelial cells. Moreover, sRAGE inhibited the psoriasin-dependent generation of ROS in endothelial cells. Finally, treatment with antioxidant Bcl-2 protein abolished the effect of psoriasin on endothelial cell proliferation. Our data suggest that psoriasin expression in mammary epithelial cells leads to increased endothelial cell proliferation in a paracrine manner through RAGE. Psoriasin may therefore play a role in breast cancer progression by promoting oxidative stress response and angiogenesis.
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detection of psoriasin s100a7 in the sera of patients with Psoriasis
British Journal of Dermatology, 2009Co-Authors: Karen S Anderson, Kornelia Polyak, J Wong, Dina Aronzon, Charlotta EnerbäckAbstract:Summary Background Psoriasis is a disease of dysregulated inflammation and epithelial hyperproliferation in the skin, involving both the innate and adaptive immune system. Psoriatic keratinocytes express high levels of psoriasin (S100A7), a small calcium-binding protein. Objectives To determine if patients with active Psoriasis have elevated serum levels of psoriasin and psoriasin-specific autoantibodies. Methods Blood was collected from 14 patients with Psoriasis vulgaris at the start of narrowband ultraviolet (UV) B therapy and from 11 of these patients every 2 weeks during the course of the UVB treatment. Patient and control sera were tested for psoriasin antigen levels by sandwich enzyme-linked immunosorbent assay, and for psoriasin autoantibody titres using recombinant purified psoriasin and overlapping peptides. Results We confirmed strong and specific expression of psoriasin in psoriatic epidermis by immunohistochemistry. Systemic psoriasin antigen levels tended to be lower in patients (mean 213 ng mL−1) than in controls (mean 331 ng mL−1, P = 0·308) and decreased with increasing disease severity. Psoriasin-specific autoantibodies were detected in a subset of patients with Psoriasis and healthy normal donors (mean 0·347 vs. 0·255 units, P = 0·246). The epitopes recognized by the autoantibodies were mapped to an external loop domain of the molecule but did not show corresponding T-cell immunogenicity. Conclusions Although psoriasin is overexpressed in psoriatic skin lesions, systemic levels of psoriasin tended to be lower with increasing disease severity, which may be due to the presence of psoriasin-specific autoantibodies. Neither psoriasin nor psoriasin-specific autoantibodies appear to be promising serum biomarkers for clinical Psoriasis.
Aleksandra Batyckabaran - One of the best experts on this subject based on the ideXlab platform.
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th17 micro milieu regulates nlrp1 dependent caspase 5 activity in skin autoinflammation
PLOS ONE, 2017Co-Authors: Aleksandra Batyckabaran, Eva Hattinger, Stephanie Zwicker, D Bureik, Andreas Schmidt, Peterarne Gerber, Simon Rothenfusser, Michel GillietAbstract:IL-1β is a potent player in cutaneous inflammation and central for the development of a Th17 micro-milieu in autoinflammatory diseases including Psoriasis. Its production is controlled at the transcriptional level and by subsequent posttranslational processing via inflammatory caspases. In this study, we detected inflammatory caspase-5 active in epidermal keratinocytes and in psoriatic skin lesions. Further, interferon-γ and interleukin-17A synergistically induced caspase-5 expression in cultured keratinocytes, which was dependent on the antimicrobial peptide psoriasin (S100A7). However, diseases-relevant triggers for caspase-5 activity and IL-1β production remain unknown. Recently, extranuclear DNA has been identified as danger-signals abundant in the psoriatic epidermis. Here, we could demonstrate that cytosolic double-stranded (ds) DNA transfected into keratinocytes triggered the activation of caspase-5 and the release of IL-1β. Further, interleukin-17A promoted caspase-5 function via facilitation of the NLRP1-inflammasome. Anti-inflammatory vitamin D interfered with the IL-1β release and suppressed caspase-5 in keratinocytes and in psoriatic skin lesions. Our data link the disease-intrinsic danger signals psoriasin (S100A7) and dsDNA for NLPR1-dependent caspase-5 activity in Psoriasis providing potential therapeutic targets in Th17-mediated skin autoinflammation.
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leukocyte derived koebnerisin s100a15 and psoriasin s100a7 are systemic mediators of inflammation in Psoriasis
Journal of Dermatological Science, 2015Co-Authors: Aleksandra Batyckabaran, Eva Hattinger, Stephanie Zwicker, Burkhard Summer, O Zack M Howard, Peter Thomas, Jacek C Szepietowski, Thomas Ruzicka, J C PrinzAbstract:Abstract Background Psoriasis is a systemic immune-mediated chronic inflammatory disease. In the skin, the antimicrobial proteins koebnerisin (S100A15) and psoriasin (S100A7) are overexpressed in the epidermis of psoriatic lesions and mediate inflammation as chemoattractants for immune cells. Their role for systemic inflammation in circulating leukocytes is unknown. Objective The aim of the study was to identify circulating leukocyte populations as a source of koebnerisin and psoriasin. Further, immune-stimulatory effects of these S100A proteins on circulating leukocytes were evaluated and their role as therapeutic response markers in patients with Psoriasis was analyzed upon UVB treatment. Methods The expression and production of koebnerisin and psoriasin by leukocytes were assessed by quantitative real-time PCR (qRT-PCR) and immunoblotting. The S100A protein mediated regulation of proinflammatory cytokines by peripheral blood mononuclear cells (PBMCs) was measured with qRT-PCR and cytometric bead assay. Results We identified circulating leukocytes as novel sources of koebnerisin (S100A15) and psoriasin (S100A7). Circulating leukocytes (PBMCs) of patients with Psoriasis produced increased levels of koebnerisin and psoriasin compared to healthy individuals. Both S100A proteins further acted as ‘alarmins’ on PBMC to induce proinflammatory cytokines implicated in the pathogenesis of Psoriasis, such as IL-1β, TNF-α, IL-6 and IL-8. Koebnerisin levels were suppressed in PBMC of psoriatic patients when effectively treated with narrow-band UVB. Conclusions Data suggest that koebnerisin and psoriasin are systemic pro-inflammatory mediators and koebnerisin acts as a therapeutic response marker in Psoriasis.
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vitamin d analog calcipotriol suppresses the th17 cytokine induced proinflammatory s100 alarmins psoriasin s100a7 and koebnerisin s100a15 in Psoriasis
Journal of Investigative Dermatology, 2012Co-Authors: Zuzana Hegyi, Aleksandra Batyckabaran, Stephanie Zwicker, Thomas Ruzicka, J C Prinz, D Bureik, Mark Peric, Sarah Koglin, Jurgen SchauberAbstract:The antimicrobial peptides (AMP) psoriasin (S100A7) and koebnerisin (S100A15) are differently induced in psoriatic skin. They act synergistically as chemoattractants and "alarmins" to amplify inflammation in Psoriasis. Th17 cytokines are key players in Psoriasis pathogenesis and vitamin D analogs feature anti-psoriatic effects; both of these activities could be mediated through epidermal AMP regulation. We show that supernatants of cultured psoriatic T cells induce and release psoriasin and koebnerisin from keratinocytes and the Th17 cytokines IL-17A, tumor necrosis factor-α, and IL-22 differently regulate psoriasin and koebnerisin reflecting their distinct expression pattern in normal and psoriatic skin. IL-17A is the principal inducer of both S100 and their expression is further amplified by cooperating Th17 cytokines in the micromilieu of psoriatic skin. Increased extracellular psoriasin and koebnerisin also synergize as "alarmins" to prime epidermal keratinocytes for production of immunotropic cytokines that further amplify the inflammatory response. Treatment of psoriatic plaques with the vitamin D analog calcipotriol interferes with the S100-mediated positive feedback loop by suppressing the increased production of psoriasin and koebnerisin in psoriatic skin and their Th17-mediated regulation in epidermal keratinocytes. Thus, targeting the S100-amplification loop could be a beneficial anti-inflammatory approach in Psoriasis and other inflammatory skin diseases.
Stephanie Zwicker - One of the best experts on this subject based on the ideXlab platform.
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th17 micro milieu regulates nlrp1 dependent caspase 5 activity in skin autoinflammation
PLOS ONE, 2017Co-Authors: Aleksandra Batyckabaran, Eva Hattinger, Stephanie Zwicker, D Bureik, Andreas Schmidt, Peterarne Gerber, Simon Rothenfusser, Michel GillietAbstract:IL-1β is a potent player in cutaneous inflammation and central for the development of a Th17 micro-milieu in autoinflammatory diseases including Psoriasis. Its production is controlled at the transcriptional level and by subsequent posttranslational processing via inflammatory caspases. In this study, we detected inflammatory caspase-5 active in epidermal keratinocytes and in psoriatic skin lesions. Further, interferon-γ and interleukin-17A synergistically induced caspase-5 expression in cultured keratinocytes, which was dependent on the antimicrobial peptide psoriasin (S100A7). However, diseases-relevant triggers for caspase-5 activity and IL-1β production remain unknown. Recently, extranuclear DNA has been identified as danger-signals abundant in the psoriatic epidermis. Here, we could demonstrate that cytosolic double-stranded (ds) DNA transfected into keratinocytes triggered the activation of caspase-5 and the release of IL-1β. Further, interleukin-17A promoted caspase-5 function via facilitation of the NLRP1-inflammasome. Anti-inflammatory vitamin D interfered with the IL-1β release and suppressed caspase-5 in keratinocytes and in psoriatic skin lesions. Our data link the disease-intrinsic danger signals psoriasin (S100A7) and dsDNA for NLPR1-dependent caspase-5 activity in Psoriasis providing potential therapeutic targets in Th17-mediated skin autoinflammation.
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leukocyte derived koebnerisin s100a15 and psoriasin s100a7 are systemic mediators of inflammation in Psoriasis
Journal of Dermatological Science, 2015Co-Authors: Aleksandra Batyckabaran, Eva Hattinger, Stephanie Zwicker, Burkhard Summer, O Zack M Howard, Peter Thomas, Jacek C Szepietowski, Thomas Ruzicka, J C PrinzAbstract:Abstract Background Psoriasis is a systemic immune-mediated chronic inflammatory disease. In the skin, the antimicrobial proteins koebnerisin (S100A15) and psoriasin (S100A7) are overexpressed in the epidermis of psoriatic lesions and mediate inflammation as chemoattractants for immune cells. Their role for systemic inflammation in circulating leukocytes is unknown. Objective The aim of the study was to identify circulating leukocyte populations as a source of koebnerisin and psoriasin. Further, immune-stimulatory effects of these S100A proteins on circulating leukocytes were evaluated and their role as therapeutic response markers in patients with Psoriasis was analyzed upon UVB treatment. Methods The expression and production of koebnerisin and psoriasin by leukocytes were assessed by quantitative real-time PCR (qRT-PCR) and immunoblotting. The S100A protein mediated regulation of proinflammatory cytokines by peripheral blood mononuclear cells (PBMCs) was measured with qRT-PCR and cytometric bead assay. Results We identified circulating leukocytes as novel sources of koebnerisin (S100A15) and psoriasin (S100A7). Circulating leukocytes (PBMCs) of patients with Psoriasis produced increased levels of koebnerisin and psoriasin compared to healthy individuals. Both S100A proteins further acted as ‘alarmins’ on PBMC to induce proinflammatory cytokines implicated in the pathogenesis of Psoriasis, such as IL-1β, TNF-α, IL-6 and IL-8. Koebnerisin levels were suppressed in PBMC of psoriatic patients when effectively treated with narrow-band UVB. Conclusions Data suggest that koebnerisin and psoriasin are systemic pro-inflammatory mediators and koebnerisin acts as a therapeutic response marker in Psoriasis.
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opposing functions of psoriasin s100a7 and koebnerisin s100a15 in epithelial carcinogenesis
Current Opinion in Pharmacology, 2013Co-Authors: Eva Hattinger, Stephanie Zwicker, Thomas Ruzicka, Stuart H Yuspa, Ronald WolfAbstract:The S100 protein family is involved in epithelial cell maturation and inflammation. Some S100 members are dysregulated during carcinogenesis and have been established as tumor markers. Psoriasin (S100A7) and koebnerisin (S100A15) are highly homologous proteins that have been first described in Psoriasis, which is characterized by disturbed epidermal maturation and chronic inflammation. Despite their homology, both S100 proteins are distinct in expression and function through different receptors but synergize as chemoattractants and pro-inflammatory ‘alarmins’ to promote inflammation. Psoriasin and koebnerisin are further regulated with tumor progression in epithelial cancers. In tumor cells, high cytoplasmic expression of psoriasin and koebnerisin may prevent oncogenic activity, whereas their nuclear translocation and extracellular secretion are associated with tumor progression and poor prognosis. The present review outlines these opposing effects of psoriasin and koebnerisin in multifunctional pathways and mechanisms that are known to affect tumor cells (‘seeds’), tumor environment (‘soil’) and tumor cell metastasis (‘seeding’) thereby influencing epithelial carcinogenesis.
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vitamin d analog calcipotriol suppresses the th17 cytokine induced proinflammatory s100 alarmins psoriasin s100a7 and koebnerisin s100a15 in Psoriasis
Journal of Investigative Dermatology, 2012Co-Authors: Zuzana Hegyi, Aleksandra Batyckabaran, Stephanie Zwicker, Thomas Ruzicka, J C Prinz, D Bureik, Mark Peric, Sarah Koglin, Jurgen SchauberAbstract:The antimicrobial peptides (AMP) psoriasin (S100A7) and koebnerisin (S100A15) are differently induced in psoriatic skin. They act synergistically as chemoattractants and "alarmins" to amplify inflammation in Psoriasis. Th17 cytokines are key players in Psoriasis pathogenesis and vitamin D analogs feature anti-psoriatic effects; both of these activities could be mediated through epidermal AMP regulation. We show that supernatants of cultured psoriatic T cells induce and release psoriasin and koebnerisin from keratinocytes and the Th17 cytokines IL-17A, tumor necrosis factor-α, and IL-22 differently regulate psoriasin and koebnerisin reflecting their distinct expression pattern in normal and psoriatic skin. IL-17A is the principal inducer of both S100 and their expression is further amplified by cooperating Th17 cytokines in the micromilieu of psoriatic skin. Increased extracellular psoriasin and koebnerisin also synergize as "alarmins" to prime epidermal keratinocytes for production of immunotropic cytokines that further amplify the inflammatory response. Treatment of psoriatic plaques with the vitamin D analog calcipotriol interferes with the S100-mediated positive feedback loop by suppressing the increased production of psoriasin and koebnerisin in psoriatic skin and their Th17-mediated regulation in epidermal keratinocytes. Thus, targeting the S100-amplification loop could be a beneficial anti-inflammatory approach in Psoriasis and other inflammatory skin diseases.
Jurgen Harder - One of the best experts on this subject based on the ideXlab platform.
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expression and regulation of antimicrobial peptide psoriasin s100a7 at the ocular surface and in the lacrimal apparatus
Investigative Ophthalmology & Visual Science, 2011Co-Authors: Fabian Garreis, Maria Gottschalt, Thomas Schlorf, Regine Glaser, Jurgen Harder, Dieter WorlitzschAbstract:PURPOSE. Psoriasin, originally isolated from Psoriasis as an over-expressed molecule of unknown function, has recently been identified as a principal Escherichia coli-killing antimicrobial peptide of healthy skin. The purpose of this study was to investigate the expression and antimicrobial role of psoriasin at the ocular surface and in the lacrimal apparatus. METHODS. Different tissues of the lacrimal apparatus and ocular surface were systematically analyzed by means of RT-PCR, Western blot, and immunohistochemistry for their ability to express and produce psoriasin. The inducibility and regulation of psoriasin were studied in human corneal as well as conjunctival epithelial cell lines after challenge with ocular pathogens and proinflammatory cytokines. Real-time RT-PCR was performed to evaluate the expression and induction of psoriasin. In addition, tear fluid obtained from different healthy volunteers was examined by ELISA for its psoriasin concentration. RESULTS. RT-PCR and Western blot analyses revealed a constitutive expression of psoriasin in cornea, conjunctiva, nasolacrimal ducts, and lacrimal gland. Immunohistochemistry showed strong staining of meibomian glands for psoriasin. No induction of psoriasin was observed after stimulation with supernatants of E. coli, whereas supernatants of Staphylococcus aureus and Haemophilus influenzae significantly increased the psoriasin mRNA expression. Stimulation with IL-1 beta and VEGF also strongly increased psoriasin transcription. The highest amounts of psoriasin protein were detected in the tear fluid (similar to 170 ng/mL) of healthy volunteers. CONCLUSIONS. The results suggest that psoriasin is produced by the structures of the ocular surface and is part of the innate immune system at the ocular surface and tear film. (Invest Ophthalmol Vis Sci. 2011;52:4914-4922) DOI:10.1167/iovs.10-6598
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enhanced expression and secretion of antimicrobial peptides in atopic dermatitis and after superficial skin injury
Journal of Investigative Dermatology, 2010Co-Authors: Jurgen Harder, Stefanie Dressel, Maike Wittersheim, Jesko Cordes, Regina Folsterholst, Ulrich Mrowietz, Ulf Meyerhoffert, Jensmichael Schroder, Ehrhardt Proksch, T. SchwarzAbstract:Human skin can defend itself against potentially invading microorganisms by production of antimicrobial peptides (AMPs). The expression of AMPs in atopic dermatitis (AD) is still emerging. To gain more insight into the role of AMPs in AD, we systematically analyzed the expression of ribonuclease 7 (RNase 7), psoriasin, and human β-defensins (hBD)-2 and -3 in AD compared with psoriatic and healthy control skin as well as after experimental barrier disruption. Immunostaining revealed enhanced expression of all AMPs in the lesional skin of untreated AD and Psoriasis when compared with non-lesional skin and controls. Accordingly, induced in vivo secretion of RNase 7, psoriasin, and hBD-2 was detected using ELISA on lesional skin in AD and in even higher concentrations in Psoriasis. The secretion of AMPs did not correlate with severity of AD and Staphylococcus aureus colonization. Skin barrier disruption caused enhanced immunoreactivity of hBD-2 and hBD-3 after 24hours. Strong secretion of RNase 7 was already detected after 1hour, whereas hBD-2 secretion was significantly enhanced after 24hours only under occlusion. Thus, a disturbed skin barrier may trigger AMP induction in AD and Psoriasis. The functional role of AMP in AD, especially with regard to the control of S. aureus colonization, needs further analysis.
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enhanced expression and secretion of antimicrobial peptides in atopic dermatitis and after superficial skin injury
Journal of Investigative Dermatology, 2010Co-Authors: Jurgen Harder, Stefanie Dressel, Maike Wittersheim, Jesko Cordes, Regina Folsterholst, Ulrich Mrowietz, Ulf Meyerhoffert, Jensmichael Schroder, Ehrhard Proksch, T. SchwarzAbstract:Human skin can defend itself against potentially invading microorganisms by production of antimicrobial peptides (AMPs). The expression of AMPs in atopic dermatitis (AD) is still emerging. To gain more insight into the role of AMPs in AD, we systematically analyzed the expression of ribonuclease 7 (RNase 7), psoriasin, and human beta-defensins (hBD)-2 and -3 in AD compared with psoriatic and healthy control skin as well as after experimental barrier disruption. Immunostaining revealed enhanced expression of all AMPs in the lesional skin of untreated AD and Psoriasis when compared with non-lesional skin and controls. Accordingly, induced in vivo secretion of RNase 7, psoriasin, and hBD-2 was detected using ELISA on lesional skin in AD and in even higher concentrations in Psoriasis. The secretion of AMPs did not correlate with severity of AD and Staphylococcus aureus colonization. Skin barrier disruption caused enhanced immunoreactivity of hBD-2 and hBD-3 after 24 hours. Strong secretion of RNase 7 was already detected after 1 hour, whereas hBD-2 secretion was significantly enhanced after 24 hours only under occlusion. Thus, a disturbed skin barrier may trigger AMP induction in AD and Psoriasis. The functional role of AMP in AD, especially with regard to the control of S. aureus colonization, needs further analysis.
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psoriatic scales a promising source for the isolation of human skin derived antimicrobial proteins
Journal of Leukocyte Biology, 2005Co-Authors: Jurgen Harder, Jensmichael SchroderAbstract:Patients with Psoriasis, a chronic, hy- perproliferative and noninfectious skin disease, suffer surprisingly fewer cutaneous infections than would be expected. This observation led us to the hypothesis that a local "chemical shield" in the form of antimicrobial proteins provides pso- riatic skin with resistance against infection. We subsequently began a systematic analysis of in vitro antimicrobially active proteins in psoriatic- scale extracts. A biochemical approach with rig- orous purification and characterization com- bined with antimicrobial testing identified a num- ber of mostly new human antibiotic peptides and proteins. In this review, we will focus on the most prominent antimicrobial proteins in psoriatic- scale extracts, which we identified as the S100- protein psoriasin, human -defensin 2 (hBD-2), RNase 7, lysozyme, and human neutrophil defen- sin 1-3. Apart from these cutaneous, antimicro- bial proteins, only a few others, including hBD-3, have been characterized. A great num- ber of minor antimicrobial proteins await further structural characterization. J. Leukoc. Biol. 77: 000 -0 00; 2005.
T. Schwarz - One of the best experts on this subject based on the ideXlab platform.
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enhanced expression and secretion of antimicrobial peptides in atopic dermatitis and after superficial skin injury
Journal of Investigative Dermatology, 2010Co-Authors: Jurgen Harder, Stefanie Dressel, Maike Wittersheim, Jesko Cordes, Regina Folsterholst, Ulrich Mrowietz, Ulf Meyerhoffert, Jensmichael Schroder, Ehrhardt Proksch, T. SchwarzAbstract:Human skin can defend itself against potentially invading microorganisms by production of antimicrobial peptides (AMPs). The expression of AMPs in atopic dermatitis (AD) is still emerging. To gain more insight into the role of AMPs in AD, we systematically analyzed the expression of ribonuclease 7 (RNase 7), psoriasin, and human β-defensins (hBD)-2 and -3 in AD compared with psoriatic and healthy control skin as well as after experimental barrier disruption. Immunostaining revealed enhanced expression of all AMPs in the lesional skin of untreated AD and Psoriasis when compared with non-lesional skin and controls. Accordingly, induced in vivo secretion of RNase 7, psoriasin, and hBD-2 was detected using ELISA on lesional skin in AD and in even higher concentrations in Psoriasis. The secretion of AMPs did not correlate with severity of AD and Staphylococcus aureus colonization. Skin barrier disruption caused enhanced immunoreactivity of hBD-2 and hBD-3 after 24hours. Strong secretion of RNase 7 was already detected after 1hour, whereas hBD-2 secretion was significantly enhanced after 24hours only under occlusion. Thus, a disturbed skin barrier may trigger AMP induction in AD and Psoriasis. The functional role of AMP in AD, especially with regard to the control of S. aureus colonization, needs further analysis.
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enhanced expression and secretion of antimicrobial peptides in atopic dermatitis and after superficial skin injury
Journal of Investigative Dermatology, 2010Co-Authors: Jurgen Harder, Stefanie Dressel, Maike Wittersheim, Jesko Cordes, Regina Folsterholst, Ulrich Mrowietz, Ulf Meyerhoffert, Jensmichael Schroder, Ehrhard Proksch, T. SchwarzAbstract:Human skin can defend itself against potentially invading microorganisms by production of antimicrobial peptides (AMPs). The expression of AMPs in atopic dermatitis (AD) is still emerging. To gain more insight into the role of AMPs in AD, we systematically analyzed the expression of ribonuclease 7 (RNase 7), psoriasin, and human beta-defensins (hBD)-2 and -3 in AD compared with psoriatic and healthy control skin as well as after experimental barrier disruption. Immunostaining revealed enhanced expression of all AMPs in the lesional skin of untreated AD and Psoriasis when compared with non-lesional skin and controls. Accordingly, induced in vivo secretion of RNase 7, psoriasin, and hBD-2 was detected using ELISA on lesional skin in AD and in even higher concentrations in Psoriasis. The secretion of AMPs did not correlate with severity of AD and Staphylococcus aureus colonization. Skin barrier disruption caused enhanced immunoreactivity of hBD-2 and hBD-3 after 24 hours. Strong secretion of RNase 7 was already detected after 1 hour, whereas hBD-2 secretion was significantly enhanced after 24 hours only under occlusion. Thus, a disturbed skin barrier may trigger AMP induction in AD and Psoriasis. The functional role of AMP in AD, especially with regard to the control of S. aureus colonization, needs further analysis.
