Jens M Schröder

Publications of Jens M Schröder

• Identification of trichohyalin-like 1, an s100 fused-type protein selectively expressed in hair follicles.

  Authors: Zhihong Wu, Ties Latendorf, Ulf Meyer-Hoffert, Jens-M Schröder

  The Journal of investigative dermatology. 05/2011; 131(8):1761-3.

• Antimicrobial peptides in healthy skin and atopic dermatitis.

  Authors: Jens-M Schröder

  Allergology international : official journal of the Japanese Society of Allergology. 01/2011; 60(1):17-24.

  Antimicrobial Peptides and Proteins (AMPs) represent effector molecules of the innate defense system in all organisms. AMPs are either constitutively or inducibly produced mainly by variousAntimicrobial Peptides and Proteins (AMPs) represent effector molecules of the innate defense system in all organisms. AMPs are either constitutively or inducibly produced mainly by various epithelial cells, including keratinocytes. This report reviews our current knowledge about the major yet known keratinocyte-derived AMPs, its role in healthy skin and atopic dermatitis.

• Purification of antimicrobial peptides from human skin.

  Authors: Jens-M Schröder

  Methods in molecular biology (Clifton, N.J.). 01/2010; 618:15-30.

  Human skin is a rich source of human antimicrobial peptides. Its cellular source is the keratinocyte, which terminally differentiates in the uppermost parts of the skin, eventually forming theHuman skin is a rich source of human antimicrobial peptides. Its cellular source is the keratinocyte, which terminally differentiates in the uppermost parts of the skin, eventually forming the stratum corneum, the horny layer. The easy availability of human stratum corneum makes it possible to identify and characterize human antimicrobial peptides with a biochemical approach. Moreover, the availability of lesional scales of patients with psoriasis, an inflammatory skin disease, allows the identification of human-inducible peptide antibiotics, which are absent in healthy skin. With this strategy, the beta-defensins hBD-2 and hBD-3, RNase-7 as well as psoriasin/S100A7 have been discovered as human antimicrobial peptides and proteins. A detailed description of the strategies and methods is presented, which allowed a successful identification and characterization of human antimicrobial peptides. We used various HPLC techniques, combined with antimicrobial testing as read-out system. In parallel, SDS-PAGE analyses as well as electrospray ionization mass spectrometry were used for further biochemical characterization as well as purity assessment.

• UV-B radiation induces the expression of antimicrobial peptides in human keratinocytes in vitro and in vivo.

  Authors: Regine Gläser, Fatemeh Navid, Winfried Schuller, Christian Jantschitsch, Jürgen Harder, Jens M Schröder, Agatha Schwarz, Thomas Schwarz

  The Journal of allergy and clinical immunology. 04/2009;

  BACKGROUND: Suppression of the adaptive immune system by UV radiation plays an important role in photocarcinogenesis. Exacerbation of skin infections has been proposed as a further consequence ofBACKGROUND: Suppression of the adaptive immune system by UV radiation plays an important role in photocarcinogenesis. Exacerbation of skin infections has been proposed as a further consequence of UV-induced immunosuppression. Clinically bacterial infections are not a problem. For defense against bacteria, the innate immune response including the release of antimicrobial peptides is much more relevant than the adaptive immune response. Keratinocytes have the capacity to release antimicrobial peptides. OBJECTIVE: We asked whether UV radiation induces antimicrobial peptides in vitro and in vivo. METHODS: Antimicrobial peptide expression by normal human keratinocytes was measured by real-time PCR and fluorescence-activated cell sorting analysis. Biopsies taken from human volunteers and skin explants were studied with immunohistochemistry. RESULTS: Real-time PCR of normal human keratinocytes revealed a dose-dependent increase of human beta-defensin-2, -3, ribonuclease 7, and psoriasin (S100A7) after UV radiation. This was confirmed at the protein level by intracellular fluorescence-activated cell sorting and in vitro immunofluorescence analysis. Immunohistochemistry of biopsies taken from healthy volunteers exposed to different UV radiation doses revealed enhanced epidermal expression of antimicrobial peptides after UV exposure. This was also confirmed by exposing human skin explants to UV radiation. CONCLUSION: UV radiation exerts diverse effects on the immune system, suppressing the adaptive but inducing the innate immune response. This may explain why T-cell-mediated immune reactions are suppressed on UV exposure but not host defense reactions against bacterial attacks.

• The Angiogenesis Inhibitor Thrombospondin-1 Inhibits Acute Cutaneous Hypersensitivity Reactions.

  Authors: Paula Velasco, Rainer Huegel, Jochen Brasch, Jens M Schröder, Michael Weichenthal, Eggert Stockfleth, Thomas Schwarz, Jack Lawler, Michael Detmar, Bernhard Lange-Asschenfeldt

  The Journal of investigative dermatology. 03/2009;

  There is increasing evidence that vascular remodeling and endothelial cell activation promote acute and chronic inflammation. Thrombospondin 1 (TSP-1) is a potent endogenous angiogenesis inhibitorThere is increasing evidence that vascular remodeling and endothelial cell activation promote acute and chronic inflammation. Thrombospondin 1 (TSP-1) is a potent endogenous angiogenesis inhibitor thought to play an important role in maintaining cutaneous vascular quiescence. We first investigated TSP-1 expression in human and contact hypersensitivity (CHS) reactions and found that TSP-1 was upregulated in the inflamed skin of patients and in mice. To elucidate the function of TSP-1 in cutaneous inflammation, we induced CHS reactions in the skin of mice with targeted epidermal TSP-1 overexpression in TSP-1-deficient mice and in wild-type mice. We found decreased edema formation, angiogenesis, and inflammatory infiltrate in the inflamed skin of TSP-1 transgenic mice. Conversely, TSP-1-deficient mice exhibited an enhanced and prolonged inflammation, characterized by increased edema formation, enhanced vascular remodeling, and increased neutrophilic infiltrate, when compared with wild-type mice. Moreover, we found strong upregulation of the proinflammatory cytokines IL-1beta, macrophage inflammatory protein 2, and tumor necrosis factor-alpha in the inflamed skin of TSP-1-deficient mice. Our results indicate that TSP-1 downregulates cutaneous delayed-type hypersensitivity reactions by acting on several distinct pathways mediating skin inflammation.Journal of Investigative Dermatology advance online publication, 5 February 2009; doi:10.1038/jid.2008.447.

• Uncovering the evolutionary history of innate immunity: The simple metazoan Hydra uses epithelial cells for host defence.

  Authors: Thomas C G Bosch, René Augustin, Friederike Anton-Erxleben, Sebastian Fraune, Georg Hemmrich, Holger Zill, Philip Rosenstiel, Gunnar Jacobs, Stefan Schreiber, Matthias Leippe, Mareike Stanisak, Joachim Grötzinger, Sascha Jung, Rainer Podschun, Joachim Bartels, Jürgen Harder, Jens M Schröder

  Developmental and comparative immunology. 12/2008;

  Although many properties of the innate immune system are shared among multicellular animals, the evolutionary origin remains poorly understood. Here we characterize the innate immune system in Hydra,Although many properties of the innate immune system are shared among multicellular animals, the evolutionary origin remains poorly understood. Here we characterize the innate immune system in Hydra, one of the simplest multicellular animals known. In the complete absence of both protective mechanical barriers and mobile phagocytes, Hydra's epithelium is remarkably well equipped with potent antimicrobial peptides to prevent pathogen infection. Induction of antimicrobial peptide production is mediated by the interaction of a leucine-rich repeats (LRRs) domain containing protein with a TIR-domain containing protein lacking LRRs. Conventional Toll-like receptors (TLRs) are absent in the Hydra genome. Our findings support the hypothesis that the epithelium represents the ancient system of host defence.

• Mouse beta-defensin-14, an antimicrobial ortholog of human beta-defensin-3.

  Authors: Kerstin Hinrichsen, Rainer Podschun, Sabine Schubert, Jens M Schröder, Jürgen Harder, Ehrhardt Proksch

  Antimicrobial agents and chemotherapy. 06/2008; 52(5):1876-9.

  Searching the database for mouse homologs of the antimicrobial peptide human beta-defensin-3 (hBD-3) revealed highest identity (69%) to mouse beta-defensin-14 (mBD-14). Recombinant mBD-14 exhibitedSearching the database for mouse homologs of the antimicrobial peptide human beta-defensin-3 (hBD-3) revealed highest identity (69%) to mouse beta-defensin-14 (mBD-14). Recombinant mBD-14 exhibited broad-spectrum, nanomolar microbicidal activity. Treatment of keratinocytes with gamma interferon or transforming growth factor alpha increased mBD-14 gene expression. These data suggest that mBD-14 is the functional ortholog of hBD-3.

• Novel anti-inflammatory properties of the angiogenesis inhibitor vasostatin.

  Authors: Rainer Huegel, Paula Velasco, Maria De La Luz Sierra, Enno Christophers, Jens M Schröder, Thomas Schwarz, Giovanna Tosato, Bernhard Lange-Asschenfeldt

  The Journal of investigative dermatology. 02/2007; 127(1):65-74.

  Endothelial cells are critically involved in the pathogenesis of inflammation, which is characterized by vasopermeability, plasma leakage, leukocyte recruitment, and neovascularization. Therefore,Endothelial cells are critically involved in the pathogenesis of inflammation, which is characterized by vasopermeability, plasma leakage, leukocyte recruitment, and neovascularization. Therefore, inhibitors of endothelial cell function could reduce inflammation. In this study, we evaluated the effects of the angiogenesis inhibitor vasostatin on inflammations induced by contact hypersensitivity reactions in mouse ears. Vasostatin-treated mice revealed significantly reduced edema formation, resulting from lower plasma leakage and inhibition of inflammation-associated vascular remodeling. Intravital microscopy studies of inflamed ears showed a decrease in the fraction of rolling leukocytes in vasostatin-treated mice, and Lycopersicon esculentum lectin-perfused ears revealed fewer leukocytes adherent to the vessel wall. The inflammatory infiltrate from vasostatin-treated mice was characterized by fewer CD8+ T cells, neutrophils, and macrophages compared to the saline-treated animals. In a modified Miles assay, vasostatin inhibited vascular endothelial growth factor-A-induced permeability, and inflamed ear tissues from vasostatin-treated mice expressed significantly reduced levels of the vascular destabilizer angiopoietin-2. These results reveal a previously unrecognized anti-inflammatory property of the angiogenesis inhibitor vasostatin, and suggest that vasostatin is a potential candidate drug for the treatment of inflammation.

• Identification of RNase 8 as a novel human antimicrobial protein.

  Authors: Bente Rudolph, Rainer Podschun, Hany Sahly, Sabine Schubert, Jens M Schröder, Jürgen Harder

  Antimicrobial agents and chemotherapy. 10/2006; 50(9):3194-6.

  The antimicrobial activity of the human RNase A superfamily member RNase 8 was evaluated. Recombinant RNase 8 exhibited broad-spectrum microbicidal activity against potential pathogenicThe antimicrobial activity of the human RNase A superfamily member RNase 8 was evaluated. Recombinant RNase 8 exhibited broad-spectrum microbicidal activity against potential pathogenic microorganisms (including multidrug-resistant strains) at micro- to nanomolar concentrations. Thus, RNase 8 was identified as a novel antimicrobial protein and may contribute to host defense.

• Immunolocalization of lactoferrin in healthy and inflamed gingival tissues.

  Authors: Jörg Eberhard, Zacharias Drosos, Markus Tiemann, Søren Jepsen, Jens M Schröder

  Journal of periodontology. 04/2006; 77(3):472-8.

  BACKGROUND: It has been reported that lactoferrin prevents biofilm formation and exerts antimicrobial activity. The aim of the present study was to evaluate the cellular source of lactoferrin inBACKGROUND: It has been reported that lactoferrin prevents biofilm formation and exerts antimicrobial activity. The aim of the present study was to evaluate the cellular source of lactoferrin in healthy and inflamed gingiva. METHODS: Lactoferrin synthesis was examined in relation to disease manifestation in biopsies of the marginal gingiva by immunohistochemistry. The expression of lactoferrin in cell cultures was studied by immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Healthy gingiva demonstrated no immunoreactivity to lactoferrin in epithelial and connective tissue cells. In inflamed specimens, lactoferrin staining was related to inflammatory cells. These results were confirmed by cell cultures of keratinocytes that did not show any immunoreactivity against lactoferrin. No mRNA message for lactoferrin was detected by RT-PCR in keratinocytes. CONCLUSIONS: These data provide evidence that lactoferrin is not synthesized in healthy gingival tissues. Therefore, elevated lactoferrin levels in the crevicular fluid of inflamed tissues originate from invading cells of the inflammatory reaction.

• Activity of human beta-defensins 2 and 3 against ESBL-producing Klebsiella strains.

  Authors: Hany Sahly, Sabine Schubert, Jürgen Harder, Michael Kleine, Dorthe Sandvang, Uwe Ullmann, Jens M Schröder, Rainer Podschun

  The Journal of antimicrobial chemotherapy. 03/2006; 57(3):562-5.

  OBJECTIVES: To test the bactericidal activity of human beta-defensins (hBDs) 2 and 3 against extended-spectrum beta-lactamase (ESBL)-producing Klebsiella strains. METHODS: Thirty-six KlebsiellaOBJECTIVES: To test the bactericidal activity of human beta-defensins (hBDs) 2 and 3 against extended-spectrum beta-lactamase (ESBL)-producing Klebsiella strains. METHODS: Thirty-six Klebsiella pneumoniae and seventeen Klebsiella oxytoca ESBL-producing isolates from nosocomial infections were tested. The bactericidal activity of recombinantly synthesized hBD-2 and -3 was tested and the results were given either as lethal doses killing > or = 90% of bacteria (LD90s) or as MBCs (> or = 99.9% killing). RESULTS: Except for one intermediately susceptible strain (MBC = 25 mg/L), all other ESBL-producing strains were highly susceptible to both defensins (LD90s and MBCs < or = 12.5 mg/L). CONCLUSIONS: The results underline the high efficacy of hBD-2 and -3 against ESBL-producing Klebsiella, making both defensins attractive candidates as antimicrobial agents to combat these increasingly troublesome bacteria.

• NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2.

  Authors: Eske Voss, Jan Wehkamp, Kai Wehkamp, Eduard F Stange, Jens M Schröder, Jürgen Harder

  The Journal of biological chemistry. 02/2006; 281(4):2005-11.

  Production of inducible antimicrobial peptides offers a first and rapid defense response of epithelial cells against invading microbes. Human beta-defensin-2 (hBD-2) is an antimicrobial peptideProduction of inducible antimicrobial peptides offers a first and rapid defense response of epithelial cells against invading microbes. Human beta-defensin-2 (hBD-2) is an antimicrobial peptide induced in various epithelia upon extracellular as well as intracellular bacterial challenge. Nucleotide-binding oligomerization domain protein 2 (NOD2/CARD15) is a cytosolic protein involved in intracellular recognition of microbes by sensing peptidoglycan fragments (e.g. muramyl dipeptide). We used luciferase as a reporter gene for a 2.3-kb hBD-2 promoter to test the hypothesis that NOD2 mediates the induction of hBD-2. Activation of NOD2 in NOD2-overexpressing human embryonic kidney 293 cells through its ligand muramyl dipeptide (MDP) induced hBD-2 expression. In contrast, overexpression of NOD2 containing the 3020insC frame-shift mutation, the most frequent NOD2 variant associated with Crohn disease, resulted in defective induction of hBD-2 through MDP. Luciferase gene reporter analyses and site-directed mutagenesis experiments demonstrated that functional binding sites for NF-kappaB and AP-1 in the hBD-2 promoter are required for NOD2-mediated induction of hBD-2 through MDP. Moreover, the NF-kappaB inhibitor Helenalin as well as a super-repressor form of the NF-kappaB inhibitor IkappaB strongly inhibited NOD2-mediated hBD-2 promoter activation. Expression of NOD2 was detected in primary keratinocytes, and stimulation of these cells with MDP induced hBD-2 peptide release. In contrast, small interference RNA-mediated down-regulation of NOD2 expression in primary keratinocytes resulted in a defective induction of hBD-2 upon MDP treatment. Together, these data suggest that NOD2 serves as an intracellular pattern recognition receptor to enhance host defense by inducing the production of antimicrobial peptides such as hBD-2.

• Human leukocyte elastase and cathepsin G are specific inhibitors of C5a-dependent neutrophil enzyme release and chemotaxis.

  Authors: Tim Tralau, Ulf Meyer-Hoffert, Jens M Schröder, Oliver Wiedow

  Experimental dermatology. 06/2004; 13(5):316-25.

  Circulating human neutrophils from patients with severe inflammatory disorders such as erysipelas and sepsis are specifically desensitized to complement factor C5a stimulation but not to stimulationCirculating human neutrophils from patients with severe inflammatory disorders such as erysipelas and sepsis are specifically desensitized to complement factor C5a stimulation but not to stimulation with other stimuli like N-formyl-methionyl-leucyl-phenylalanine (FMLP), interleukin-8 (IL-8), leukotriene B4 (LTB4), or platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine). In this study, we raised the question whether factors released from polymorphonuclear leukocytes (PMNs) can specifically down-regulate C5a-dependent neutrophil functions. When neutrophils were preincubated with either neutrophil lysates or neutrophil degranulation supernatants, a complete inhibition of C5a-stimulated beta-glucuronidase release and chemotaxis could be observed, whereas FMLP-, IL-8-, LTB4- or PAF-dependent functions were not affected. Serine protease inhibitors like phenylmethylsulfonyl fluoride, antileukoprotease, or elafin abolished this effect. High-performance liquid chromatography of neutrophil degranulation supernatants revealed pronounced inhibition of C5a-dependent neutrophil functions in fractions exerting elastase or cathepsin G activity, but not in fractions exerting proteinase 3 activity. Using purified human leukocyte elastase (HLE), C5a responses like intracellular calcium influx, beta-glucuronidase release, and chemotaxis were also specifically inhibited. Our experiments show that the release of HLE or cathepsin G from neutrophils specifically down-regulates the responsiveness of neutrophils to C5a. Elastase and cathepsin G may therefore play an important role in the down-regulation of acute inflammation.

• Th2- and to a lesser extent Th1-type cytokines upregulate the production of both CXC (IL-8 and gro-alpha) and CC (RANTES, eotaxin, eotaxin-2, MCP-3 and MCP-4) chemokines in human airway epithelial cells.

  Authors: Ulf Meyer-Hoffert, Diana Lezcano-Meza, Joachim Bartels, Aurea Rosalia Montes-Vizuet, Jens M Schröder, Luis M Teran

  International archives of allergy and immunology. 09/2003; 131(4):264-71.

  BACKGROUND: Both CXC and CC chemokines play an important role in leukocyte recruitment. However, a systematic examination of their production by human airway epithelial cells (HAECs) has not beenBACKGROUND: Both CXC and CC chemokines play an important role in leukocyte recruitment. However, a systematic examination of their production by human airway epithelial cells (HAECs) has not been carried out. The objective of this study was to investigate whether Th1- and Th2-type cytokines regulate chemokine production in HAECs. METHODS: HAECs were grown from both nasal and bronchial tissue and subsequently stimulated with either Th1- or Th2-type cytokines. RESULTS: Constitutive mRNA expression for gro-alpha, IL-8 and RANTES was seen in both human nasal and human bronchial epithelial cells. IL-4 was the strongest stimulus for both gene expression and protein production of the chemokines RANTES, IL-8 and gro-alpha, while both IL-13 and IFN-gamma were weaker inducers of these chemokines, with the exception of gro-alpha (IL-13 was a strong stimulus for gro-alpha production). TNF-alpha synergized with IL-4, and to a lesser extent with IFN-gamma and IL-13, to release RANTES, IL-8 and gro-alpha. IL-4 and to a lesser extent IL-13 and IFN-gamma stimulated the production of MCP-3 and -4, eotaxin and eotaxin-2 immunoreactivities. However, no induction of the mRNAs encoding these chemokines was observed, suggesting that they may be released from a preformed pool within the HAECs. CONCLUSION: These findings suggest that when released into the airways, Th2- and to a lesser extent Th1-type cytokines may stimulate recruitment of eosinophils and neutrophils through the release of CC (RANTES, MCP-3 and -4, eotaxin and eotaxin-2) and CXC chemokines (gro-alpha and IL-8).

• The role of the Duffy antigen-related chemokine receptor in psoriasis vulgaris.

  Authors: Michael Sticherling, Claudia Baisch, Erika Bornscheuer, Jens M Schröder, Enno Christophers

  Cytokine. 07/2002; 18(6):329-33.

  Chemokines represent a family of potent biological mediators. Within the group of receptors mediating their effects, a promiscuous receptor has been found which is able to bind and inactivate diverseChemokines represent a family of potent biological mediators. Within the group of receptors mediating their effects, a promiscuous receptor has been found which is able to bind and inactivate diverse chemokines of both C-C and C-X-C families. It is co-localized with blood group antigens of the Duffy system on the same glycoprotein and expressed on red blood cells as well as post-capillary blood vessels. In the present study three aspects of Duffy pathophysiology were studied: firstly the amount of IL-8 and RANTES binding to red blood cells and its correlation to disease activity of psoriatic patients, secondly the distribution of Duffy phenotype among psoriatic patients and thirdly the expression of Duffy antigen in normal vs psoriatic skin. Red blood cells from psoriatic patients (n=50) were lysed by triton X (1%) and supernatants tested in IL-8- and RANTES sandwich-ELISA. Duffy phenotype of psoriatic patients (n=50) was assessed by typing red blood cells with specific antisera in indirect Coombs technique. For immunohistochemical detection in normal and psoriatic skin (n=10 respectively) a specific monoclonal antibody (Fy6) was used. Neither IL-8- nor RANTES-levels on red blood cells correlated to disease activity and distribution of Duffy phenotype in psoriatics was not significantly altered when compared to the normal population. Furthermore, Duffy antigen was expressed in a similar pattern in normal and psoriatic skin at all parts of vasculature, albeit much more abundantly in diseased skin. Altogether, chemokine binding to red blood cells seems of minor importance in psoriasis. However, Duffy antigen together with other binding mechanisms like proteoglycans may play a role at local level by binding locally produced chemokines. Thus biological effects of chemokines are both restricted and focussed to dermal tissue.

• The novel human beta-defensin-3 is widely expressed in oral tissues.

  Authors: Anton Dunsche, Yahya Açil, Henrik Dommisch, Reiner Siebert, Jens M Schröder, Søren Jepsen

  European journal of oral sciences. 05/2002; 110(2):121-4.

  The purpose of this study was to investigate the expression of human beta-defensins (hBD), especially of the recently discovered hBD-3, in oral tissues by reverse-transcription polymerase chainThe purpose of this study was to investigate the expression of human beta-defensins (hBD), especially of the recently discovered hBD-3, in oral tissues by reverse-transcription polymerase chain reaction (RT-PCR). Primary oral keratinocytes (n = 3) and fibroblasts (n = 3), 64 non-inflamed and 40 inflamed oral tissue samples, and 10 samples of salivary glands, were examined. The transcripts for hBD-3 (61/64), as well as for hBD-1 (64/64) and hBD-2 (54/64), were found to be widely expressed in non-inflamed oral tissues. In contrast, only 23, 22 and 24 of the 40 inflamed tissues showed detectable hBD-1, -2 and -3 transcripts, respectively. In salivary glands, mRNA expression was constitutive for hBD-1, frequent for hBD-2 (9/10), and infrequent for hBD-3 (4/10). Oral keratinocytes, but not fibroblasts, contained transcripts for all beta-defensins, suggesting that the novel hBD-3 is also produced in the epithelial compartment of oral tissues. The results indicate an important role for the novel hBD-3, as well as for hBD-1 and hBD-2, in the innate oral epithelial host defense.

• Neutrophil-activating peptide 1/interleukin 8 mRNA expression and protein secretion by human monocytes: Effect of cyclosporin A

  Authors: Ulrich Mrowietz, Michael Sticherling, Volker Mielke, Jens-M. Schröder, Enno Christophers

  Cytokine.

  Neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8) is a recently described cytokine with potent chemotactic activity for human neutrophil granulocytes (PMN) and T cells. In psoriasis, aNeutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8) is a recently described cytokine with potent chemotactic activity for human neutrophil granulocytes (PMN) and T cells. In psoriasis, a chronic hyperproliferative and inflammatory skin disorder, PMN and T cells are found as prominent cells in the inflammatory infiltrate of the lesions; however, monocytes were shown to be the first cells invading a newly formed plaque. NAP-1/IL-8 was found to be present in high amounts in the skin and in scale material of psoriatic patients. Psoriasis responds well to systemic treatment with cyclosporin A (CsA), an immunosuppressive peptide. Therefore, we addressed the question of whether the clinical improvement of psoriatic patients during CsA therapy may be due to an inhibition of NAP-1/IL-8 production and secretion from monocytes. Purified human monocytes were stimulated by lipopolysaccharide in the presence or absence of various concentrations of CsA. Production of NAP-1/IL-8 was determined as expression of specific mRNA by fluorescent in situ hybridization. Secreted peptide was measured by bioassay (PMN chemotaxis) and enzyme-linked immunosorbent assay (ELISA) using specific monoclonal antibodies. The results show that CsA neither inhibited mRNA expression for NAP-1/IL-8 nor secretion of the peptide. These findings support the hypothesis that the pharmacological effect of CsA may be restricted to the inhibition of T-cell activation and proliferation.

• Uncovering the evolutionary history of innate immunity: The simple metazoan Hydra uses epithelial cells for host defence

  Authors: Thomas C.G. Bosch, René Augustin, Friederike Anton-Erxleben, Sebastian Fraune, Georg Hemmrich, Holger Zill, Philip Rosenstiel, Gunnar Jacobs, Stefan Schreiber, Matthias Leippe, Mareike Stanisak, Joachim Grötzinger, Sascha Jung, Rainer Podschun, Joachim Bartels, Jürgen Harder, Jens-M. Schröder

  Developmental & Comparative Immunology.

  Although many properties of the innate immune system are shared among multicellular animals, the evolutionary origin remains poorly understood. Here we characterize the innate immune system in Hydra,Although many properties of the innate immune system are shared among multicellular animals, the evolutionary origin remains poorly understood. Here we characterize the innate immune system in Hydra, one of the simplest multicellular animals known. In the complete absence of both protective mechanical barriers and mobile phagocytes, Hydra’s epithelium is remarkably well equipped with potent antimicrobial peptides to prevent pathogen infection. Induction of antimicrobial peptide production is mediated by the interaction of a leucine-rich repeats (LRRs) domain containing protein with a TIR-domain containing protein lacking LRRs. Conventional Toll-like receptors (TLRs) are absent in the Hydra genome. Our findings support the hypothesis that the epithelium represents the ancient system of host defence.

• THE ROLE OF THE DUFFY ANTIGEN-RELATED CHEMOKINE RECEPTOR IN PSORIASIS VULGARIS

  Authors: Michael Sticherling, Claudia Baisch, Erika Bornscheuer, Jens-M. Schröder, Enno Christophers

  Cytokine.

  Chemokines represent a family of potent biological mediators. Within the group of receptors mediating their effects, a promiscuous receptor has been found which is able to bind and inactivate diverseChemokines represent a family of potent biological mediators. Within the group of receptors mediating their effects, a promiscuous receptor has been found which is able to bind and inactivate diverse chemokines of both C-C and C-X-C families. It is co-localized with blood group antigens of the Duffy system on the same glycoprotein and expressed on red blood cells as well as post-capillary blood vessels. In the present study three aspects of Duffy pathophysiology were studied: firstly the amount of IL-8 and RANTES binding to red blood cells and its correlation to disease activity of psoriatic patients, secondly the distribution of Duffy phenotype among psoriatic patients and thirdly the expression of Duffy antigen in normal vs psoriatic skin. Red blood cells from psoriatic patients (n=50) were lysed by triton X (1%) and supernatants tested in IL-8- and RANTES sandwich-ELISA. Duffy phenotype of psoriatic patients (n=50) was assessed by typing red blood cells with specific antisera in indirect Coombs technique. For immunohistochemical detection in normal and psoriatic skin (n=10 respectively) a specific monoclonal antibody (Fy6) was used. Neither IL-8- nor RANTES-levels on red blood cells correlated to disease activity and distribution of Duffy phenotype in psoriatics was not significantly altered when compared to the normal population. Furthermore, Duffy antigen was expressed in a similar pattern in normal and psoriatic skin at all parts of vasculature, albeit much more abundantly in diseased skin. Altogether, chemokine binding to red blood cells seems of minor importance in psoriasis. However, Duffy antigen together with other binding mechanisms like proteoglycans may play a role at local level by binding locally produced chemokines. Thus biological effects of chemokines are both restricted and focussed to dermal tissue.