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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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Psoriasin and CD24 demonstrate a similar staining pattern in DCIS.
2013Co-Authors: Jenny Vegfors, Stina Petersson, Kornelia Polyak, Aniko Kovacs, Charlotta EnerbäckAbstract:The expression patterns of Psoriasin and CD24 in ductal carcinoma in situ (DCIS) were analyzed by immunohistochemisty. Psoriasin and CD24 showed an extremely intense staining and a similar staining pattern in DCIS. A Psoriasin staining was observed in the cytoplasm and the nucleus of the cells. B CD24 staining was observed in the cytoplasm, the nucleus and in the membranes of the mammary epithelial cells. The figures illustrate representative examples of Psoriasin and CD24 expression in the same DCIS tumor.
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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: E. 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.
Stina Petersson - One of the best experts on this subject based on the ideXlab platform.
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Psoriasin and CD24 demonstrate a similar staining pattern in DCIS.
2013Co-Authors: Jenny Vegfors, Stina Petersson, Kornelia Polyak, Aniko Kovacs, Charlotta EnerbäckAbstract:The expression patterns of Psoriasin and CD24 in ductal carcinoma in situ (DCIS) were analyzed by immunohistochemisty. Psoriasin and CD24 showed an extremely intense staining and a similar staining pattern in DCIS. A Psoriasin staining was observed in the cytoplasm and the nucleus of the cells. B CD24 staining was observed in the cytoplasm, the nucleus and in the membranes of the mammary epithelial cells. The figures illustrate representative examples of Psoriasin and CD24 expression in the same DCIS tumor.
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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: E. 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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s100a7 Psoriasin highly expressed in ductal carcinoma in situ dcis is regulated by ifn gamma in mammary epithelial cells
BMC Cancer, 2007Co-Authors: Stina Petersson, Anna Bylander, Maria Yhr, Charlotta EnerbäckAbstract:Background The aim of the present work was to explore signal transduction pathways used in the regulation of S100A7 (Psoriasin). Members of the S100 gene family participate in many important cellular functions. Psoriasin, S100A8 (calgranulin A) and S100A9 (calgranulin B) are expressed in ductal carcinoma in situ (DCIS), as well as in the hyperproliferative skin disease, psoriasis. In the latter condition, a disturbance in the STAT pathway has recently been reported. This pathway is implicated in the regulation of IFN-gamma, widely recognized as a key cytokine in psoriasis. IFN-gamma also exerts anti-tumor action in a number of tumor cell types, including breast cancer. We therefore examined the effect of IFN-gamma and STAT-signaling on the Psoriasin expression.
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s100a7 Psoriasin highly expressed in ductal carcinoma in situ dcis is regulated by ifn gamma in mammary epithelial cells
BMC Cancer, 2007Co-Authors: Stina Petersson, Anna Bylander, Maria Yhr, Charlotta EnerbäckAbstract:The aim of the present work was to explore signal transduction pathways used in the regulation of S100A7 (Psoriasin). Members of the S100 gene family participate in many important cellular functions. Psoriasin, S100A8 (calgranulin A) and S100A9 (calgranulin B) are expressed in ductal carcinoma in situ (DCIS), as well as in the hyperproliferative skin disease, psoriasis. In the latter condition, a disturbance in the STAT pathway has recently been reported. This pathway is implicated in the regulation of IFN-gamma, widely recognized as a key cytokine in psoriasis. IFN-gamma also exerts anti-tumor action in a number of tumor cell types, including breast cancer. We therefore examined the effect of IFN-gamma and STAT-signaling on the Psoriasin expression. We established a TAC2 mouse mammary epithelial cell line with tetracycline-inducible Psoriasin expression (Tet-Off). Viability in cell culture was estimated using MTS assay. Protein and gene expression were evaluated by Western blotting and quantitative real-time PCR. Statistical analyses were assessed using a one-tailed, paired t-test. We report the downregulation of Psoriasin by IFN-gamma in the MDA-MB-468 breast cancer cell line, as well as the downregulation of Psoriasin induced by anoikis in cell lines derived from different epithelial tissues. In contrast, IFN-gamma had no suppressive effect on calgranulin A or calgranulin B. IFN-gamma is an important activator of the STAT1 pathway and we confirmed an active signaling pathway in the cell lines that responded to IFN-gamma treatment. In contrast, in the SUM190 breast carcinoma cell line, IFN-gamma did not suppress the expression of endogenous Psoriasin. Moreover, a reduced phosphorylation of the STAT1 protein was observed. We showed that IFN-gamma treatment and the inhibition of the transcription factor NFkappaB had a synergistic effect on Psoriasin levels. Finally, in TAC2 cells with tetracycline-induced Psoriasin expression, we observed the increased viability of Psoriasin-expressing cells after IFN-gamma treatment. Our data support the possibility that Psoriasin expression is transcriptionally suppressed by IFN-gamma and that this effect is likely to be mediated by the activation of the STAT1 signaling pathway. The increased viability of Psoriasin-expressing cells after IFN-gamma exposure suggests that Psoriasin expression leads to the development of an apoptosis-resistant phenotype.
Alberto Civetta - One of the best experts on this subject based on the ideXlab platform.
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expression analysis of the mouse s100a7 Psoriasin gene in skin inflammation and mammary tumorigenesis
BMC Cancer, 2005Co-Authors: Meghan Webb, Ethan Emberley, Michael Lizardo, Salem Alowami, Gefei Qing, Abdullah Alfiaar, Linda J Snellcurtis, Yulian Niu, Alberto CivettaAbstract:The human Psoriasin (S100A7) gene has been implicated in inflammation and tumor progression. Implementation of a mouse model would facilitate further investigation of its function, however little is known of the murine Psoriasin gene. In this study we have cloned the cDNA and characterized the expression of the potential murine ortholog of human S100A7/Psoriasin in skin inflammation and mammary tumorigenesis. On the basis of chromosomal location, phylogenetic analysis, amino acid sequence similarity, conservation of a putative Jab1-binding motif, and similarities of the patterns of mouse S100A7/Psoriasin gene expression (measured by RT-PCR and in-situ hybridization) with those of human S100A7/Psoriasin, we propose that mouse S100A7/Psoriasin is the murine ortholog of human Psoriasin/S100A7. Although mouse S100A7/Psoriasin is poorly conserved relative to other S100 family members, its pattern of expression parallels that of the human Psoriasin gene. In murine skin S100A7/Psoriasin was significantly upregulated in relation to inflammation. In murine mammary gland expression is also upregulated in mammary tumors, where it is localized to areas of squamous differentiation. This mirrors the context of expression in human tumor types where both squamous and glandular differentiation occur, including cervical and lung carcinomas. Additionally, mouse S100A7/Psoriasin possesses a putative Jab1 binding motif that mediates many downstream functions of the human S100A7 gene. These observations and results support the hypothesis that the mouse S100A7 gene is structurally and functionally similar to human S100A7 and may offer a relevant model system for studying its normal biological function and putative role in tumor progression.
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expression analysis of the mouse s100a7 Psoriasin gene in skin inflammation and mammary tumorigenesis
BMC Cancer, 2005Co-Authors: Meghan Webb, Ethan Emberley, Michael Lizardo, Salem Alowami, Gefei Qing, Abdullah Alfiaar, Linda J Snellcurtis, Yulian Niu, Alberto CivettaAbstract:Background The human Psoriasin (S100A7) gene has been implicated in inflammation and tumor progression. Implementation of a mouse model would facilitate further investigation of its function, however little is known of the murine Psoriasin gene. In this study we have cloned the cDNA and characterized the expression of the potential murine ortholog of human S100A7/Psoriasin in skin inflammation and mammary tumorigenesis.
Jurgen Harder - One of the best experts on this subject based on the ideXlab platform.
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Psoriasin key molecule of the cutaneous barrier
Journal Der Deutschen Dermatologischen Gesellschaft, 2011Co-Authors: Regine Glaser, Maike Wittersheim, Bente Koten, Jurgen HarderAbstract:Psoriasin (S100 A7) was discovered two decades ago as a protein abundantly expressed in psoriatic keratinocytes. Even though much scientific research has been carried out on the characterization of Psoriasin, only recent studies point to an important role of Psoriasin as an antimicrobial and immunomodulatory protein in skin and other epithelia. In this review, we provide an overview of the major findings in Psoriasin research and discuss novel studies highlighting the role of Psoriasin as an important effector molecule of the cutaneous barrier.
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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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the antimicrobial protein Psoriasin s100a7 is upregulated in atopic dermatitis and after experimental skin barrier disruption
Journal of Investigative Dermatology, 2009Co-Authors: Regine Glaser, Maike Wittersheim, Jesko Cordes, Regina Folsterholst, Ulf Meyerhoffert, Jensmichael Schroder, Jurgen Harder, Ehrhardt Proksch, Julia Kobliakova, T. SchwarzAbstract:The innate defense of the skin against microbial threats is influenced by antimicrobial proteins (AMP). Staphylococcus aureus often colonizes the skin of patients with atopic dermatitis (AD). This was explained by diminished expression of AMP including cathelicidin/LL-37, human β-defensins-2 and -3, and dermcidin. The S100-protein Psoriasin is an additional keratinocyte-derived AMP that preferentially kills E. coli. As E. coli infections are not observed in atopic skin we investigated the functional role of Psoriasin in AD patients. Immunohistochemistry demonstrated enhanced epidermal Psoriasin expression in AD. An up to 1500-fold increase in secreted Psoriasin was detected by ELISA in vivo on the surface of AD skin compared to healthy control skin. Surprisingly, tumor necrosis factor-α-enhanced Psoriasin release in primary keratinocytes was inhibited by the Th2-cytokines IL-4 and -13, whereas IL-17 and -22 induced Psoriasin. Epidermal barrier disruption significantly enhanced Psoriasin expression as demonstrated by tape stripping in healthy volunteers. The upregulation of Psoriasin in AD maybe induced by the disrupted skin barrier offering a possible explanation why these patients do not suffer from skin infections with E. coli. This indicates that the antimicrobial response in AD is not generally impaired, but greatly differs according to the type of AMP produced by the skin.
Jurgen Schauber - One of the best experts on this subject based on the ideXlab platform.
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Vitamin D analogs differentially control antimicrobial peptide/“alarmin” expression in psoriasis
2013Co-Authors: Mark Peric, Thomas Ruzicka, Sarah Koglin, Yvonne Dombrowski, Katrin Gross, Eva Bradac, Amanda S Buchau, Ulrich Zugel, Jurgen SchauberAbstract:Antimicrobial peptides (AMPs) are strongly expressed in lesional skin in psoriasis and play an important role as proinflammatory ‘‘alarmins’ ’ in this chronic skin disease. Vitamin D analogs like calcipotriol have antipsoriatic effects and might mediate this effect by changing AMP expression. In this study, keratinocytes in lesional psoriatic plaques showed decreased expression of the AMPs b-defensin (HBD) 2 and HBD3 after topical treatment with calcipotriol. At the same time, calcipotriol normalized the proinflammatory cytokine milieu and decreased interleukin (IL)-17A, IL-17F and IL-8 transcript abundance in lesional psoriatic skin. In contrast, cathelicidin antimicrobial peptide expression was increased by calcipotriol while Psoriasin expression remained unchanged. In cultured human epidermal keratinocytes the effect of different vitamin D analogs on the expression of AMPs was further analyzed. All vitamin D analogs tested blocked IL-17A induced HBD2 expression by increasing IkB-a protein and inhibition of NF-kB signaling. At the same time vitamin D analogs induced cathelicidin through activation of the vitamin D receptor and MEK/ERK signaling. These studies suggest that vitamin D analogs differentially alter AMP expression in lesional psoriatic skin and cultured keratinocytes. Balancing AMP ‘‘alarmin’
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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.
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vitamin d analogs differentially control antimicrobial peptide alarmin expression in psoriasis
PLOS ONE, 2009Co-Authors: Mark Peric, Thomas Ruzicka, Sarah Koglin, Yvonne Dombrowski, Katrin Gross, Eva Bradac, Amanda S Buchau, Andreas Steinmeyer, Ulrich Zugel, Jurgen SchauberAbstract:Antimicrobial peptides (AMPs) are strongly expressed in lesional skin in psoriasis and play an important role as proinflammatory “alarmins” in this chronic skin disease. Vitamin D analogs like calcipotriol have antipsoriatic effects and might mediate this effect by changing AMP expression. In this study, keratinocytes in lesional psoriatic plaques showed decreased expression of the AMPs β-defensin (HBD) 2 and HBD3 after topical treatment with calcipotriol. At the same time, calcipotriol normalized the proinflammatory cytokine milieu and decreased interleukin (IL)-17A, IL-17F and IL-8 transcript abundance in lesional psoriatic skin. In contrast, cathelicidin antimicrobial peptide expression was increased by calcipotriol while Psoriasin expression remained unchanged. In cultured human epidermal keratinocytes the effect of different vitamin D analogs on the expression of AMPs was further analyzed. All vitamin D analogs tested blocked IL-17A induced HBD2 expression by increasing IκB-α protein and inhibition of NF-κB signaling. At the same time vitamin D analogs induced cathelicidin through activation of the vitamin D receptor and MEK/ERK signaling. These studies suggest that vitamin D analogs differentially alter AMP expression in lesional psoriatic skin and cultured keratinocytes. Balancing AMP “alarmin” expression might be a novel goal in treatment of chronic inflammatory skin diseases.
