@article{KosnopfelSinnbergSaueretal.2020,
  author    = {Kosnopfel, Corinna and Sinnberg, Tobias and Sauer, Birgit and Niessner, Heike and Muenchow, Alina and Fehrenbacher, Birgit and Schaller, Martin and Mertens, Peter R. and Garbe, Claus and Thakur, Basant Kumar and Schittek, Birgit},
  title     = {Tumour progression stage-dependent secretion of YB-1 stimulates melanoma cell migration and invasion},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {8},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12082328},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211206},
  year      = {2020},
  abstract  = {Secreted factors play an important role in intercellular communication. Therefore, they are not only indispensable for the regulation of various physiological processes but can also decisively advance the development and progression of tumours. In the context of inflammatory disease, Y-box binding protein 1 (YB-1) is actively secreted and the extracellular protein promotes cell proliferation and migration. In malignant melanoma, intracellular YB-1 expression increases during melanoma progression and represents an unfavourable prognostic marker. Here, we show active secretion of YB-1 from melanoma cells as opposed to benign cells of the skin. Intriguingly, YB-1 secretion correlates with the stage of melanoma progression and depends on a calcium- and ATP-dependent non-classical secretory pathway leading to the occurrence of YB-1 in the extracellular space as a free protein. Along with an elevated YB-1 secretion of melanoma cells in the metastatic growth phase, extracellular YB-1 exerts a stimulating effect on melanoma cell migration, invasion, and tumourigenicity. Collectively, these data suggest that secreted YB-1 plays a functional role in melanoma cell biology, stimulating metastasis, and may serve as a novel biomarker in malignant melanoma that reflects tumour aggressiveness.},
  language  = {en}
}
@article{CorreiaSantosBischlerWestermannetal.2021,
  author    = {Correia Santos, Sara and Bischler, Thorsten and Westermann, Alexander J. and Vogel, J{\"o}rg},
  title     = {MAPS integrates regulation of actin-targeting effector SteC into the virulence control network of Salmonella small RNA PinT},
  series = {Cell Reports},
  volume    = {34},
  journal   = {Cell Reports},
  number    = {5},
  doi       = {10.1016/j.celrep.2021.108722},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259134},
  pages     = {108722},
  year      = {2021},
  abstract  = {A full understanding of the contribution of small RNAs (sRNAs) to bacterial virulence demands knowledge of their target suites under infection-relevant conditions. Here, we take an integrative approach to capturing targets of the Hfq-associated sRNA PinT, a known post-transcriptional timer of the two major virulence programs of Salmonella enterica. Using MS2 affinity purification and RNA sequencing (MAPS), we identify PinT ligands in bacteria under in vitro conditions mimicking specific stages of the infection cycle and in bacteria growing inside macrophages. This reveals PinT-mediated translational inhibition of the secreted effector kinase SteC, which had gone unnoticed in previous target searches. Using genetic, biochemical, and microscopic assays, we provide evidence for PinT-mediated repression of steC mRNA, eventually delaying actin rearrangements in infected host cells. Our findings support the role of PinT as a central post-transcriptional regulator in Salmonella virulence and illustrate the need for complementary methods to reveal the full target suites of sRNAs.},
  language  = {en}
}
@article{BachmannEhlertBeckeretal.2020,
  author    = {Bachmann, Julia and Ehlert, Elias and Becker, Matthias and Otto, Christoph and Radeloff, Katrin and Blunk, Torsten and Bauer-Kreisel, Petra},
  title     = {Ischemia-like stress conditions stimulate trophic activities of adipose-derived stromal/stem cells},
  series = {Cells},
  volume    = {9},
  journal   = {Cells},
  number    = {9},
  issn      = {2073-4409},
  doi       = {10.3390/cells9091935},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211233},
  year      = {2020},
  abstract  = {Adipose-derived stromal/stem cells (ASCs) have been shown to exert regenerative functions, which are mainly attributed to the secretion of trophic factors. Upon transplantation, ASCs are facing an ischemic environment characterized by oxygen and nutrient deprivation. However, current knowledge on the secretion capacity of ASCs under such conditions is limited. Thus, the present study focused on the secretory function of ASCs under glucose and oxygen deprivation as major components of ischemia. After exposure to glucose/oxygen deprivation, ASCs maintained distinct viability, but the metabolic activity was greatly reduced by glucose limitation. ASCs were able to secrete a broad panel of factors under glucose/oxygen deprivation as revealed by a cytokine antibody array. Quantification of selected factors by ELISA demonstrated that glucose deprivation in combination with hypoxia led to markedly higher secretion levels of the angiogenic and anti-apoptotic factors IL-6, VEGF, and stanniocalcin-1 as compared to the hypoxic condition alone. A conditioned medium of glucose/oxygen-deprived ASCs promoted the viability and tube formation of endothelial cells, and the proliferation and migration of fibroblasts. These findings indicate that ASCs are stimulated by ischemia-like stress conditions to secrete trophic factors and would be able to exert their beneficial function in an ischemic environment.},
  language  = {en}
}
@article{SchwarzRemerNahrendorfetal.2013,
  author    = {Schwarz, Tobias and Remer, Katharina A. and Nahrendorf, Wiebke and Masic, Anita and Siewe, Lisa and M{\"u}ller, Werner and Roers, Axel and Moll, Heidrun},
  title     = {T Cell-Derived IL-10 Determines Leishmaniasis Disease Outcome and Is Suppressed by a Dendritic Cell Based Vaccine},
  series = {PLoS Pathogens},
  volume    = {9},
  journal   = {PLoS Pathogens},
  number    = {6},
  doi       = {10.1371/journal.ppat.1003476},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130385},
  pages     = {e1003476},
  year      = {2013},
  abstract  = {Abstract In the murine model of Leishmania major infection, resistance or susceptibility to the parasite has been associated with the development of a Th1 or Th2 type of immune response. Recently, however, the immunosuppressive effects of IL-10 have been ascribed a crucial role in the development of the different clinical correlates of Leishmania infection in humans. Since T cells and professional APC are important cellular sources of IL-10, we compared leishmaniasis disease progression in T cell-specific, macrophage/neutrophil-specific and complete IL-10-deficient C57BL/6 as well as T cell-specific and complete IL-10-deficient BALB/c mice. As early as two weeks after infection of these mice with L. major, T cell-specific and complete IL-10-deficient animals showed significantly increased lesion development accompanied by a markedly elevated secretion of IFN-γ or IFN-γ and IL-4 in the lymph nodes draining the lesions of the C57BL/6 or BALB/c mutants, respectively. In contrast, macrophage/neutrophil-specific IL-10-deficient C57BL/6 mice did not show any altered phenotype. During the further course of disease, the T cell-specific as well as the complete IL-10-deficient BALB/c mice were able to control the infection. Furthermore, a dendritic cell-based vaccination against leishmaniasis efficiently suppresses the early secretion of IL-10, thus contributing to the control of parasite spread. Taken together, IL-10 secretion by T cells has an influence on immune activation early after infection and is sufficient to render BALB/c mice susceptible to an uncontrolled Leishmania major infection. Author Summary The clinical symptoms caused by infections with Leishmania parasites range from self-healing cutaneous to uncontrolled visceral disease and depend not only on the parasite species but also on the type of the host's immune response. It is estimated that 350 million people worldwide are at risk, with a global incidence of 1-1.5 million cases of cutaneous and 500,000 cases of visceral leishmaniasis. Murine leishmaniasis is the best-characterized model to elucidate the mechanisms underlying resistance or susceptibility to Leishmania major parasites in vivo. Using T cell-specific and macrophage-specific mutant mice, we demonstrate that abrogating the secretion of the immunosuppressive cytokine IL-10 by T cells is sufficient to render otherwise susceptible mice resistant to an infection with the pathogen. The healing phenotype is accompanied by an elevated specific inflammatory immune response very early after infection. We further show that dendritic cell-based vaccination against leishmaniasis suppresses the early secretion of IL-10 following challenge infection. Thus, our study unravels a molecular mechanism critical for host immune defense, aiding in the development of an effective vaccine against leishmaniasis.},
  language  = {en}
}
@article{ArndtHoffackerZellmeretal.2014,
  author    = {Arndt, Andreas and Hoffacker, Peter and Zellmer, Konstantin and Goecer, Oktay and Recks, Mascha S. and Kuerten, Stefanie},
  title     = {Conventional Housing Conditions Attenuate the Development of Experimental Autoimmune Encephalomyelitis},
  series = {PLoS ONE},
  volume    = {9},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0099794},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119603},
  pages     = {e99794},
  year      = {2014},
  abstract  = {BACKGROUND: The etiology of multiple sclerosis (MS) has remained unclear, but a causative contribution of factors outside the central nervous system (CNS) is conceivable. It was recently suggested that gut bacteria trigger the activation of CNS-reactive T cells and the development of demyelinative disease. METHODS: C57BL/6 (B6) mice were kept either under specific pathogen free or conventional housing conditions, immunized with the myelin basic protein (MBP)-proteolipid protein (PLP) fusion protein MP4 and the development of EAE was clinically monitored. The germinal center size of the Peyer's patches was determined by immunohistochemistry in addition to the level of total IgG secretion which was assessed by ELISPOT. ELISPOT assays were also used to measure MP4-specific T cell and B cell responses in the Peyer's patches and the spleen. Ear swelling assays were performed to determine the extent of delayed-type hypersensitivity reactions in specific pathogen free and conventionally housed mice. RESULTS: In B6 mice that were actively immunized with MP4 and kept under conventional housing conditions clinical disease was significantly attenuated compared to specific pathogen free mice. Conventionally housed mice displayed increased levels of IgG secretion in the Peyer's patches, while the germinal center formation in the gut and the MP4-specific TH17 response in the spleen were diminished after immunization. Accordingly, these mice displayed an attenuated delayed type hypersensitivity (DTH) reaction in ear swelling assays. CONCLUSIONS: The data corroborate the notion that housing conditions play a substantial role in the induction of murine EAE and suggest that the presence of gut bacteria might be associated with a decreased immune response to antigens of lower affinity. This concept could be of importance for MS and calls for caution when considering the therapeutic approach to treat patients with antibiotics."},
  language  = {en}
}
@article{ZhangVanCrombruggenHoltappelsetal.2014,
  author    = {Zhang, Nan and Van Crombruggen, Koen and Holtappels, Gabriele and Lan, Feng and Katotomichelakis, Michail and Zhang, Luo and H{\"o}gger, Petra and Bachert, Claus},
  title     = {Suppression of Cytokine Release by Fluticasone Furoate vs. Mometasone Furoate in Human Nasal Tissue Ex-Vivo},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {4},
  doi       = {10.1371/journal.pone.0093754},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116779},
  pages     = {e93754},
  year      = {2014},
  abstract  = {Background: Topical glucocorticosteroids are the first line therapy for airway inflammation. Modern compounds with higher efficacy have been developed, but head-to-head comparison studies are sparse. Objective: To compare the activity of two intranasal glucocorticoids, fluticasone furoate (FF) and mometasone furoate (MF) with respect to the inhibition of T helper (Th)1, Th2 and Th17 cytokine release in airway mucosa. Methods: We used an ex-vivo human nasal mucosal tissue model and employed pre-and post-Staphylococcus aureus enterotoxin B (SEB)-challenge incubations with various time intervals and drug concentrations to mimic typical clinical situations of preventive or therapeutic use. Results: At a fixed concentration of 10(-10) M, FF had significantly higher suppressive effects on interferon (IFN)-gamma,interleukin (IL)-2 and IL-17 release, but not IL-5 or tumor necrosis factor (TNF)-alpha, vs. MF. While the maximal suppressive activity was maintained when FF was added before or after tissue stimulation, the cytokine suppression capacity of MF appeared to be compromised when SEB-induced cell activation preceded the addition of the drug. In a pre-challenge incubation setting with removal of excess drug concentrations, MF approached inhibition of IL-5 and TNF-alpha after 6 and 24 hours while FF maximally blocked the release of these cytokines right after pre-incubation. Furthermore, FF suppressed a wider range of T helper cytokines compared to MF. Conclusion: The study demonstrates the potential of our human mucosal model and shows marked differences in the ability to suppress the release of various cytokines in pre-and post-challenge settings between FF and MF mimicking typical clinical situations of preventive or therapeutic use.},
  language  = {en}
}