Ingrid Moll

Publications (44)192.17 Total impact

• Article: Contribution of Tight Junction Proteins to Ion, Macromolecule, and Water Barrier in Keratinocytes.

  Nina Kirschner, Rita Rosenthal, Mikio Furuse, Ingrid Moll, Michael Fromm, Johanna M Brandner
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  ABSTRACT: Tight junctions (TJs) form a selective barrier for ions, water, and macromolecules in simple epithelia. In keratinocytes and epidermis, TJs were shown to be involved in individual barrier functions. The absence of the TJ protein claudin-1 (Cldn1) in mice results in a skin-barrier defect characterized by lethal water loss. However, detailed molecular analyses of the various TJ barriers in keratinocytes and the contribution of distinct TJ proteins are missing. Herein, we discriminate TJ-dependent paracellular resistance from transcellular resistance in cultured keratinocytes using the two-path impedance spectroscopy. We demonstrate that keratinocyte TJs form a barrier for Na(+), Cl(-), and Ca(2+), and contribute to barrier function for water and larger molecules of different size. In addition, knockdown of Cldn1, Cldn4, occludin, and zonula occludens-1 increased paracellular permeabilities for ions and larger molecules, demonstrating that all of these TJ proteins contribute to barrier formation. Remarkably, Cldn1 and Cldn4 are not critical for TJ barrier function for water in submerged keratinocyte cultures. However, Cldn1 influences stratum corneum (SC) proteins important for SC water barrier function, and is crucial for TJ barrier formation for allergen-sized macromolecules.Journal of Investigative Dermatology advance online publication, 14 February 2013; doi:10.1038/jid.2012.507.
  Journal of Investigative Dermatology 02/2013; · 6.31 Impact Factor
• Source

  Available from: Michael Mildner

  Article: Occludin is involved in adhesion, apoptosis, differentiation and ca(2+)-homeostasis of human keratinocytes: implications for tumorigenesis.

  Susanne Rachow, Michaela Zorn-Kruppa, Ulrich Ohnemus, Nina Kirschner, Sabine Vidal-Y-Sy, Peter von den Driesch, Christian Börnchen, Jürgen Eberle, Michael Mildner, Eik Vettorazzi, Rita Rosenthal, Ingrid Moll, Johanna M Brandner
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  ABSTRACT: Tight junction (TJ) proteins are involved in a number of cellular functions, including paracellular barrier formation, cell polarization, differentiation, and proliferation. Altered expression of TJ proteins was reported in various epithelial tumors. Here, we used tissue samples of human cutaneous squamous cell carcinoma (SCC), its precursor tumors, as well as sun-exposed and non-sun-exposed skin as a model system to investigate TJ protein alteration at various stages of tumorigenesis. We identified that a broader localization of zonula occludens protein (ZO)-1 and claudin-4 (Cldn-4) as well as downregulation of Cldn-1 in deeper epidermal layers is a frequent event in all the tumor entities as well as in sun-exposed skin, suggesting that these changes result from chronic UV irradiation. In contrast, SCC could be distinguished from the precursor tumors and sun-exposed skin by a frequent complete loss of occludin (Ocln). To elucidate the impact of down-regulation of Ocln, we performed Ocln siRNA experiments in human keratinocytes and uncovered that Ocln downregulation results in decreased epithelial cell-cell adhesion and reduced susceptibility to apoptosis induction by UVB or TNF-related apoptosis-inducing ligand (TRAIL), cellular characteristics for tumorigenesis. Furthermore, an influence on epidermal differentiation was observed, while there was no change of E-cadherin and vimentin, markers for epithelial-mesenchymal transition. Ocln knock-down altered Ca(2+)-homeostasis which may contribute to alterations of cell-cell adhesion and differentiation. As downregulation of Ocln is also seen in SCC derived from other tissues, as well as in other carcinomas, we suggest this as a common principle in tumor pathogenesis, which may be used as a target for therapeutic intervention.
  PLoS ONE 01/2013; 8(2):e55116. · 4.09 Impact Factor
• Article: Tight junctions and differentiation--a chicken or the egg question?

  Nina Kirschner, Rita Rosenthal, Dorothee Günzel, Ingrid Moll, Johanna M Brandner
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  ABSTRACT: Skin barrier function is indispensable to prevent the uncontrolled loss of water and solutes and to protect the body from external assaults. To fulfil this function, keratinocytes undergo a complex pathway of differentiation that terminates in the formation of the stratum corneum. Additionally, tight junctions (TJs), which are cell-cell junctions localized in the stratum granulosum, are involved in the barrier function of the skin. Important biological and clinical roles of TJs are strongly suggested by altered TJ protein levels and distribution in skin diseases like psoriasis, ichthyosis and atopic dermatitis. Because these skin diseases show alterations in differentiation and TJs, it was suggested that changes in TJs might simply be a consequence of altered differentiation. However, in this viewpoint, we like to argue that the situation is not as simple and depends on the specific microenvironment. We discuss three hypotheses regarding the interplay between TJs/TJ proteins and differentiation: (1) TJs/TJ proteins are influenced by differentiation, (2) differentiation is influenced by TJs/TJ proteins, and (3) TJs/TJ proteins and differentiation are independent of each other. In addition, the concept is introduced that both processes are going on at the same time, which means that while one specific TJ protein/barrier component might be influenced by differentiation, the other may influence differentiation.
  Experimental Dermatology 03/2012; 21(3):171-5. · 3.54 Impact Factor
• Article: Cutaneous malakoplakia.

  Michael Sormes, Ute Siemann-Harms, Johanna M Brandner, Ingrid Moll
  Journal der Deutschen Dermatologischen Gesellschaft 09/2011; 9(11):914-5. · 1.47 Impact Factor
• Article: Major translocation of calcium upon epidermal barrier insult: imaging and quantification via FLIM/Fourier vector analysis.

  Martin J Behne, Susana Sanchez, Nicholas P Barry, Nina Kirschner, Wilfried Meyer, Theodora M Mauro, Ingrid Moll, Enrico Gratton
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  ABSTRACT: Calcium controls an array of key events in keratinocytes and epidermis: localized changes in Ca(2+) concentrations and their regulation are therefore especially important to assess when observing epidermal barrier homeostasis and repair, neonatal barrier establishment, in differentiation, signaling, cell adhesion, and in various pathological states. Yet, tissue- and cellular Ca(2+) concentrations in physiologic and diseased states are only partially known, and difficult to measure. Prior observations on the Ca(2+) distribution in skin were based on Ca(2+) precipitation followed by electron microscopy, or proton-induced X-ray emission. Neither cellular and/or subcellular localization could be determined through these approaches. In cells in vitro, fluorescent dyes have been used extensively for ratiometric measurements of static and dynamic Ca(2+) concentrations, also assessing organelle Ca(2+) concentrations. For lack of better methods, these findings together build the basis for the current view of the role of Ca(2+) in epidermis, their limitations notwithstanding. Here we report a method using Calcium Green 5N as the calcium sensor and the phasor-plot approach to separate raw lifetime components. Thus, fluorescence lifetime imaging (FLIM) enables us to quantitatively assess and visualize dynamic changes of Ca(2+) at light-microscopic resolution in ex vivo biopsies of unfixed epidermis, in close to in vivo conditions. Comparing undisturbed epidermis with epidermis following a barrier insult revealed major shifts, and more importantly, a mobilization of high amounts of Ca(2+) shortly following barrier disruption, from intracellular stores. These results partially contradict the conventional view, where barrier insults abrogate a Ca(2+) gradient towards the stratum granulosum. Ca(2+) FLIM overcomes prior limitations in the observation of epidermal Ca(2+) dynamics, and will allow further insights into basic epidermal physiology.
  Archives for Dermatological Research 03/2011; 303(2):103-15. · 2.28 Impact Factor
• Article: Expression of keratins in cutaneous epithelial tumors and related disorders--distribution and clinical significance.

  Ichiro Kurokawa, Kenzo Takahashi, Ingrid Moll, Roland Moll
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  ABSTRACT: Keratins are a highly diverse family of cytoskeletal proteins and important markers of epithelial cell differentiation. In this review, applying the new keratin nomenclature recently introduced, we summarize and discuss the distribution and significance of keratin patterns in cutaneous epithelial tumors in relation to the epithelial structures of normal human skin. The available literature data show that the analysis of keratin profiles broadens our understanding of the differentiation, nature and histogenetic origin of the various, highly singular epithelial tumors arising in the skin. Moreover, keratins may aid in histological diagnosis and, in certain instances, may be helpful for the recognition of tumor malignancy and aggressiveness. Furthermore, we briefly address the topic of keratin-related skin disorders.
  Experimental Dermatology 03/2011; 20(3):217-28. · 3.54 Impact Factor
• Article: CD44 Regulates Tight-Junction Assembly and Barrier Function

  Nina Kirschner, Marek Haftek, Carien M Niessen, Martin J Behne, Mikio Furuse, Ingrid Moll, Johanna M Brandner
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  ABSTRACT: Upon barrier disturbance, adult CD44 knockout (KO) mice show delayed recovery of epidermal barrier function. This correlates with the loss of apical polarization of lamellar body (LB) secretion. As tight junctions (TJs) are crucial for barrier function and regulate polarized targeting of vesicles, we hypothesized that CD44 regulates TJs and associated cell polarity complexes, which in turn contributes to altered skin barrier function in CD44 KO mice. We show a delay in embryonic barrier formation associated with a loss of apical LB localization in CD44 KO mice, which correlates with alterations in TJ proteins and Par3. Simultaneously, the activity of Rac1, a major regulator of TJ barrier function, was reduced. Importantly, normalization of barrier function at E18.5 coincided with the recovery of these proteins. Tape-stripping experiments revealed that the loss of CD44 also affected TJ proteins upon induced disturbance of the barrier in adult mice. In CD44 KO keratinocytes, cell polarization and TJ barrier function were impaired. An alteration of differentiation markers was also observed, but was less pronounced than alterations of TJ proteins. Taken together, the results reveal an important function for CD44 in the assembly and function of TJs, suggesting their involvement in the skin barrier phenotype of CD44 KO mice.Abbreviations: AJ, adherens junction; aPKC, atypical protein kinase C; CK, cytokeratin; Cldn, claudin; DAPI, 4′,6-diamidino-2-phenylindole; GEF, guanine nucleotide exchange factor; HA, hyaluronic acid; HA-L, large-size hyaluronic acid; KO, knockout; LB, lamellar body; PBS, phosphate-buffered saline; PTF, paracellular tracer flux; RT, room temperature; rtPCR, real-time PCR; SG, stratum granulosum; TER, transepithelial resistance; TEWL, transepidermal water loss; TJ, tight junction; WT, wild type; ZO, zonula occludens
  Journal of Investigative Dermatology 12/2010; 131(4):932-943. · 6.31 Impact Factor
• Article: Tight junctions form a barrier in human epidermis.

  Nina Kirschner, Pia Houdek, Michael Fromm, Ingrid Moll, Johanna M Brandner
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  ABSTRACT: Tight junctions (TJ) are cell-cell junctions that have proved to form a paracellular barrier for solutes and water between cells of epithelia, including the stratum granulosum of the stratified epithelium of the epidermis of newborn mice. In mice lacking claudin-1, a major barrier-forming TJ component, this barrier was abolished. However, the role of TJ in human skin is controversially discussed as unambiguous data were missing so far. Here, we investigated TJ barrier function in healthy human skin as well as in skin samples from psoriatic lesions which are characterized by an altered localization of TJ proteins. We demonstrate for human skin that occludin- and claudin-1-positive sites in the stratum granulosum form a barrier for extracellular biotin-SH (557Da) and that in psoriatic skin the localization of the barrier and the TJ proteins are altered in parallel.
  European journal of cell biology 11/2010; 89(11):839-42. · 3.31 Impact Factor
• Source

  Available from: Catherine Wright

  Article: Connexin 43 mimetic peptide Gap27 reveals potential differences in the role of Cx43 in wound repair between diabetic and non-diabetic cells.

  Simone Pollok, Ann-Catherine Pfeiffer, Ralf Lobmann, Catherine S Wright, Ingrid Moll, Patricia E M Martin, Johanna M Brandner
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  ABSTRACT: During early wound healing (WH) events Connexin 43 (Cx43) is down-regulated at wound margins. In chronic wound margins, including diabetic wounds, Cx43 expression is enhanced suggesting that down-regulation is important for WH. We previously reported that the Cx43 mimetic peptide Gap27 blocks Cx43 mediated intercellular communication and promotes skin cell migration of infant cells in vitro. In the present work we further investigated the molecular mechanism of Gap27 action and its therapeutic potential to improve WH in skin tissue and diabetic and non-diabetic cells. Ex vivo skin, organotypic models and human keratinocytes/fibroblasts of young and old donors and of diabetic and non-diabetic origin were used to assess the impact of Gap27 on cell migration, proliferation, Cx43 expression, localization, phosphorylation and hemichannel function. Exposure of ex vivo WH models to Gap27 decreased dye spread, accelerated WH and elevated cell proliferation. In non-diabetic cell cultures Gap27 decreased dye uptake through Cx hemichannels and after scratch wounding cells showed enhanced migration and proliferation. Cells of diabetic origin were less susceptible to Gap27 during early passages. In late passages these cells showed responses comparable to non-diabetic cells. The cause of the discrepancy between diabetic and non-diabetic cells correlated with decreased Cx hemichannel activity in diabetic cells but excluded differences in Cx43 expression, localization and Ser368-phosphorylation. These data emphasize the importance of Cx43 in WH and support the concept that Gap27 could be a beneficial therapeutic to accelerate normal WH. However, its use in diabetic WH may be restricted and our results highlight differences in the role of Cx43 in skin cells of different origin.
  Journal of Cellular and Molecular Medicine 03/2010; 15(4):861-73. · 4.13 Impact Factor
• Article: Alteration of tight junction proteins is an early event in psoriasis: putative involvement of proinflammatory cytokines.

  Nina Kirschner, Claudia Poetzl, Peter von den Driesch, Ewa Wladykowski, Ingrid Moll, Martin J Behne, Johanna M Brandner
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  ABSTRACT: Psoriasis is an inflammatory skin disease characterized by hyperproliferation of keratinocytes, impaired barrier function, and pronounced infiltration of inflammatory cells. Tight junctions (TJs) are cell-cell junctions that form paracellular barriers for solutes and inflammatory cells. Altered localization of TJ proteins in the epidermis was described in plaque-type psoriasis. Here we show that localization of TJ proteins is already altered in early-stage psoriasis. Occludin, ZO-1, and claudin-4 are found in more layers than in normal epidermis, and claudin-1 and -7 are down-regulated in the basal and in the uppermost layers. In plaque-type psoriasis, the staining patterns of occludin and ZO-1 do not change, whereas the claudins are further down-regulated. Near transmigrating granulocytes, all TJ proteins except for junctional adhesion molecule-A are down-regulated. Treatment of cultured keratinocytes with interleukin-1beta and tumor necrosis factor-alpha, which are present at elevated levels in psoriatic skin, results in an increase of transepithelial resistance at early time points and a decrease at later time points. Injection of interleukin-1beta into an ex vivo skin model leads to an up-regulation of occludin and ZO-1, resembling TJ protein alteration in early psoriasis. Our results show for the first time that alteration of TJ proteins is an early event in psoriasis and is not the consequence of the more profound changes found in plaque-type psoriasis. Our data indicate that cytokines are involved in alterations of TJ proteins observed in psoriasis.
  American Journal Of Pathology 09/2009; 175(3):1095-106. · 4.89 Impact Factor
• Article: Evidence for distinct populations of human Merkel cells.

  A-C Eispert, F Fuchs, J M Brandner, P Houdek, E Wladykowski, Ingrid Moll
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  ABSTRACT: Merkel cells (MCs) are neuroendocrine cells of unknown origin located in the skin. They are identified at electron microscopic level by electron dense granules, at light microscopic level by the presence of cytokeratins 8, 18, 19 and 20. Contradictory reports concerning the presence of other molecules of epithelial as well as neural origin prompted us to investigate whether there are distinct populations of human MCs. Here, we show the heterogeneous expression of villin, N-CAM, NGF-R, and neurofilaments in MCs. Synaptophysin is found in all MCs but with different intensity, nestin is absent. Expression patterns vary between interfollicular epidermis, hair follicles and glabrous epidermis. We conclude that there are distinct populations of MCs, but all populations contain markers for epithelial as well as neural cells. Putative functions of the distinct populations are discussed.
  Histochemie 04/2009; 132(1):83-93. · 2.59 Impact Factor
• Article: CD34(+) fibrocytes in melanocytic nevi and malignant melanomas of the skin.

  Cordula Wessel, Christina C Westhoff, Katharina Nowak, Ingrid Moll, Peter J Barth
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  ABSTRACT: CD34(+) fibrocytes are constitutive elements of the human connective tissue. The stroma associated with invasive carcinomas is characterized by a stereotypic loss of CD34(+) fibrocytes and a phenotype change towards CD34(-) alpha-Smooth muscle actin (SMA)(+) myofibroblasts. Secreted protein acidic and rich in cysteine (SPARC) is an important mediator of tumor-associated stromal remodeling. Melanocytic lesions of the skin have not been investigated as to this aspect up to now. Thus, we investigated a total of 20 malignant melanomas and 29 melanocytic nevi. The normal dermis and benign melanocytic nevi showed numerous CD34(+) fibrocytes, whereas malignant melanomas were devoid of this cell type. alpha-SMA-positive myofibroblasts were absent from the normal dermis, melanocytic nevi, and malignant melanomas. SPARC was positive in malignant melanoma cells and negative in their associated stroma, while all melanocytic nevi were completely negative. The stromal phenotype of malignant melanomas (CD34(-) alpha-SMA(-)) differs from that of invasive carcinomas (CD34(-) alpha-SMA(+)) suggesting different pathogenic mechanisms involved in tumor-associated stromal remodeling. SPARC expression appears to be closely related to malignancy in melanocytic lesions.
  Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 10/2008; 453(5):485-9. · 2.49 Impact Factor
• Article: Regulation of epidermal tight-junctions (TJ) during infection with exfoliative toxin-negative Staphylococcus strains.

  Ulrich Ohnemus, Klaas Kohrmeyer, Pia Houdek, Holger Rohde, Ewa Wladykowski, Sabine Vidal, Matthias A Horstkotte, Martin Aepfelbacher, Nina Kirschner, Martin J Behne, Ingrid Moll, Johanna M Brandner
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  ABSTRACT: Tight Junction (TJ) proteins have been shown to exert a barrier function within the skin. Here, we study the fate of TJ proteins during the challenge of the skin by bacterial colonization and infection. We investigated the influence of various exfoliative toxin-negative Staphylococcus strains on TJ, adherens junction (AJ), desmosomal proteins, and actin in a human keratinocyte infection culture and in a porcine skin infection model. We found that the pathogen Staphylococcus aureus downregulates TJ and subsequently AJ and desmosomal proteins, including atypical protein kinase C, an essential player in TJ formation, at the cell-cell borders of keratinocytes in a time and concentration dependent manner. Little changes in protein and RNA levels were seen, indicating redistribution of proteins. In cultured keratinocytes, a reduction of transepithelial resistance was observed. Staphylococcus epidermidis shows only minor effects. All strains induced enhanced expression of occludin and ZO-1 at the beginning of colonization/infection. Thus, we demonstrate that TJ are likely to be involved in skin infection of exfoliative toxin-negative S. aureus. As we did not find a change in actin, and as changes of TJ preceded alterations of AJs and desmosomes, we suggest that S. aureus targets TJ.
  Journal of Investigative Dermatology 05/2008; 128(4):906-16. · 6.31 Impact Factor
• Article: Expression of matrix metalloproteinases, cytokines, and connexins in diabetic and nondiabetic human keratinocytes before and after transplantation into an ex vivo wound-healing model.

  Johanna M Brandner, Steffi Zacheja, Pia Houdek, Ingrid Moll, Ralf Lobmann
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  ABSTRACT: Wound healing is known to require a well-organized balance of numerous factors, e.g., cytokines, matrix metalloproteinases (MMPs), and their inhibitors, as well as direct cell-cell communication (connexins). Disruption of this balance may lead to the formation of chronic wounds such as diabetic foot ulcers. The transplantation of autologous keratinocytes is a promising therapy for diabetic foot ulcers; however, little is known about their characteristics on a molecular level. Therefore, we intended to characterize transplanted keratinocytes from diabetic and nondiabetic origin before and after transplantation. We isolated human keratinocytes from diabetic and nondiabetic origins and transplanted them into an ex vivo wound healing model. To characterize the keratinocytes, we investigated mRNA expression of MMP-1, MMP-2, and MMP-9; tissue inhibitor of MMP (TIMP)-1 and TIMP-2; interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha; Cx26 (connexin 26) and Cx43; and, for connexins, immunolocalization. We found no significantly increased expression of the molecules investigated in cultured keratinocytes from diabetic compared with nondiabetic origin, even though there were significant differences for MMP-2, IL-1beta, and TNF-alpha in skin biopsies. Expression of IL-1beta was significantly lower in keratinocytes from diabetic origin. In the course of wound healing, differences in the dynamics of expression of MMP-1, IL-1beta, and Cx43 were observed. Our results suggest that keratinocytes from diabetic origin are as capable for transplantation into chronic wounds as keratinocytes from healthy origin at the starting point of therapy. However, differences in expression dynamics later on might reflect the systemic influence of diabetes resulting in a memory of the transplanted keratinocytes.
  Diabetes care 02/2008; 31(1):114-20. · 8.09 Impact Factor
• Article: The different structures containing tight junction proteins in epidermal and other stratified epithelial cells, including squamous cell metaplasia.

  Holger Schlüter, Ingrid Moll, Hartwig Wolburg, Werner W Franke
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  ABSTRACT: In stratified squamous epithelia constituent proteins of tight junctions (TJs) are not restricted to the zonula occludens-related structures of the uppermost living cell layer such as the stratum granulosum of the epidermis but TJ membrane proteins such as occludin and certain members of the claudin family as well as TJ plaque proteins, notably cingulin and protein ZO-1, have also been identified by immunofluorescence and immunoelectron microscopy in more basal layers where they form special cell-cell-connecting structures such as the "lamellated" and the "sandwich" junctions. In the present study, we describe another TJ protein-containing structure, the very small puncta occludentia ("stud junctions"), as the smallest identifiable TJ-like unit that occurs in most, perhaps all strata. We have also determined the specific distributions of TJ proteins in the cell layers of squamous cell metaplasias of the human bronchial tract. Moreover, we show that the occludin-related tetraspanin protein tricellulin-alpha connects and seals the membranes of adjacent "three corner" cell structures of the uppermost layer in keratinocytes growing in culture. We hypothesize the possible occurrence of tricellulin-beta in more basal cell layers of keratinocyte cultures and the general occurrence of different tricellulin splice forms in stratified epithelia in situ, and discuss the possible functions of TJ proteins in stratified epithelia and tumors derived therefrom.
  European Journal of Cell Biology 01/2008; 86(11-12):645-55. · 2.81 Impact Factor
• Article: Biphasic regulation of AP-1 subunits during human epidermal wound healing.

  Angela Neub, Pia Houdek, Ulrich Ohnemus, Ingrid Moll, Johanna M Brandner
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  ABSTRACT: Cutaneous wound healing is a well-coordinated process that includes inflammation, proliferation, and differentiation. Activator protein 1 (AP-1) subunits have been implicated in the regulation of genes important for these processes and have been shown to be involved in wound healing. However, investigation of human healing and non-healing wounds in vivo and ex vivo, and the comparative analysis of several members of the Jun and Fos families are still missing. Here, we show that normal human epidermal wound healing is biphasic. In the first phase all AP-1 subunits investigated, that is c-Jun, Jun B, Jun D, c-Fos, and Fos B are absent from the nuclei at the wound margins/leading edges. This downregulation coincides with that of the gap junction protein connexin 43. Later on, c-Jun, Jun B, Jun D, and c-Fos reappear in the nuclei of the leading edges in a time-dependent manner. In non-healing wounds, a more intensive staining of keratinocytes at the wound margins is often observed. Our findings suggest that coordinated down- and upregulation of the various AP-1 subunits in the course of epidermal wound healing is important for its undisturbed progress, putatively by influencing inflammation and cell-cell communication.
  Journal of Investigative Dermatology 11/2007; 127(10):2453-62. · 6.31 Impact Factor
• Article: Glycoconjugate profiling of primary melanoma and its sentinel node and distant metastases: implications for diagnosis and pathophysiology of metastases.

  Anka Thies, Anke Berlin, Georg Brunner, Hans-Joachim Schulze, Ingrid Moll, Uwe Pfüller, Christoph Wagener, Melitta Schachner, Peter Altevogt, Udo Schumacher
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  ABSTRACT: Aiming at more precise detection of melanoma cells in sentinel lymph nodes and better understanding of the mechanisms underlying metastatic spread, expression of L1, CEACAM1, and binding of the lectins HPA, ML-I and PNA, was assessed in benign nevi (n=12), primary melanomas (PTs: n=67), their corresponding sentinel lymph nodes (SLNs: n=40), and distant metastases (DMs: n=35). Sensitivity and specificity of CEACAM1 (95-97%; 66%) and L1 (90-93%; 100%) exceeded that of the standard markers MelanA, S100, and HMB45 in single marker use. Lectin binding was found in PTs and DMs (HPA: 69% and 77%; ML-I: 82% and 77%, respectively), but rarely in SLNMs (HPA: 20%, ML-I: 20%, PNA: 5%, respectively). The highly specific and sensitive L1-11A against L1 and 4D1/C2 against CEACAM1 antibodies are a worthy completion to standard antibody panels for diagnosis of melanoma cells. Both CAMs seem to be functionally involved in lymphatic and haematogenous spread, and are thus promising target molecules for immunotoxins.
  Cancer Letters 05/2007; 248(1):68-80. · 4.24 Impact Factor
• Article: A Thai patient with generalised inflammatory skin disease 18 years after migration to Europe.

  Stefan Schmiedel, Stephan Ehrhardt, Ingrid Moll, Gerd D Burchard
  The Lancet 05/2006; 367(9520):1458. · 38.28 Impact Factor
• Article: Anti-proliferative effect of peroxisome proliferator-activated receptor gamma agonists on human malignant melanoma cells in vitro.

  Christian Freudlsperger, Ingrid Moll, Udo Schumacher, Anka Thies
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  ABSTRACT: Malignant melanoma has a poor reputation for early spread and no curative treatment is yet available. As peroxisome proliferator-activated receptor gamma (PPARgamma) agonists (glitazones) have recently been shown to have growth-inhibiting effects on different cancer lineages, the aim of this study was to analyze the effects of four glitazones (rosiglitazone, ciglitazone, pioglitazone and troglitazone) on the growth of six human malignant melanoma cells in vitro. Proliferation of six human melanoma cell lines under glitazone treatment over a broad concentration range (0.15-300 micromol/l) was assessed by means of the XTT cell proliferation assay, and expression of PPARgamma in these cell lines was analyzed using both immunohistochemical and molecular biological techniques. All four glitazones showed a significant dose-dependent anti-proliferative effect on all six cell lines starting at a concentration of 0.3 micromol/l, with ciglitazone being the most potent inhibitor of cell growth, followed by troglitazone, rosiglitazone and pioglitazone. PPARgamma was predominantly localized in the cytoplasm; however, there were quantitative differences in PPARgamma expression between the different cell lines as demonstrated by quantification of Western blots. As an already approved class of drugs, glitazones have been found to significantly inhibit growth of human malignant melanoma cells in vitro and might be a promising tool for further therapeutic studies.
  Anti-Cancer Drugs 04/2006; 17(3):325-32. · 2.41 Impact Factor
• Source

  Available from: Nikolas Haass

  Article: Differential induction of connexins 26 and 30 in skin tumors and their adjacent epidermis.

  Nikolas K Haass, Ewa Wladykowski, Sabine Kief, Ingrid Moll, Johanna M Brandner
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  ABSTRACT: Gap junctions (GJs) have been shown to play a role in tumor progression including a variety of keratinocyte-derived and non-keratinocyte-derived skin tumors. Here we show that the synthesis of the GJ proteins connexin 26 and connexin 30 (Cx26 and Cx30) is induced in keratinocyte-derived epithelial skin tumors whereas there is either no change or a downregulation of Cx43. Cx26, Cx30, and Cx43 are absent in non-epithelial skin tumors. Further, Cx26 and Cx30 are induced in the epidermis adjacent to malignant melanoma but absent in the epidermis adjacent to benign non-epithelial skin lesions (melanocytic nevi and angioma). The keratinocyte-derived skin tumors are very heterogeneous regarding the Cx26/Cx30 pattern in the epidermis at the periphery of the tumors. We did not observe any difference in the localization of the very similar proteins Cx26 and Cx30 but a variation in intensity of immunoreactivity. As the staining patterns of Cx26 and Cx30 antibodies are not identical to those of CK6, a marker for hyperproliferation, and CK17, a marker for trauma, we discuss that the induction of these gap junctional proteins exceeds a reflection of reactive hyperproliferative or traumatized epidermis. We further discuss the putative roles of these gap junctional proteins in tumor progression.
  Journal of Histochemistry and Cytochemistry 03/2006; 54(2):171-82. · 2.72 Impact Factor