Background: Epidermal hyperplasia represents a morphologic hallmark of psoriatic skin lesions. Langerhans cells (LCs) in the psoriatic epidermis engage with keratinocytes (KCs) in tight physical interactions; moreover, they induce T-cell-mediated immune responses critical to psoriasis. Objective: This study sought to improve the understanding of epidermal factors in psoriasis pathogenesis.Methods: BMP7-LCs versus TGF-b1-LCs were phenotypically characterized and their functional properties were analyzed using flow cytometry, cell kinetic studies, co-culture with CD4 T cells, and cytokine measurements. Furthermore, immunohistology of healthy and psoriatic skin was performed. Additionally, in vivo experiments with Jun f/f JunB f/f K5cre-ER T mice were carried out to assess the From a the
Background: Bone morphogenetic proteins (BMPs) are members of the TGF-b family that signal via the BMP receptor (BMPR) signaling cascade, distinct from canonical TGF-b signaling. BMP downstream signaling is strongly induced within epidermal keratinocytes in cutaneous psoriatic lesions, and BMP7 instructs monocytic cells to acquire characteristics of psoriasis-associated Langerhans dendritic cells (DCs). Regulatory T (Treg)-cell numbers strongly increase during psoriatic skin inflammation and were recently shown to limit psoriatic skin inflammation. However, the factors mediating Treg-cell accumulation in psoriatic skin currently remain unknown. Objective: We sought to investigate the role of BMP signaling in Treg-cell accumulation in psoriasis. Methods: The following methods were used: immunohistology of patients and healthy controls; ex vivo models of Treg-cell generation in the presence or absence of Langerhans cells; analysis of BMP versus canonical TGF-b signaling in DCs and Treg cells; and modeling of psoriatic skin inflammation in mice lacking the BMPR type 1a in CD11c 1 cells. Results: We here demonstrated a positive correlation between Treg-cell numbers and epidermal BMP7 expression in cutaneous psoriatic lesions and show that unlike Treg cells from healthy skin, a portion of inflammation-associated Treg cells exhibit constitutive-active BMP signaling. We further found
BackgroundOverexpression the KCNJ3, a gene that encodes subunit 1 of G-protein activated inwardly rectifying K+ channel (GIRK1) in the primary tumor has been found to be associated with reduced survival times and increased lymph node metastasis in breast cancer patients.MethodsIn order to survey possible tumorigenic properties of GIRK1 overexpression, a range of malignant mammary epithelial cells, based on the MCF-7 cell line that permanently overexpress different splice variants of the KCNJ3 gene (GIRK1a, GIRK1c, GIRK1d and as a control, eYFP) were produced. Subsequently, selected cardinal neoplasia associated cellular parameters were assessed and compared.ResultsAdhesion to fibronectin coated surface as well as cell proliferation remained unaffected. Other vital parameters intimately linked to malignancy, i.e. wound healing, chemoinvasion, cellular velocities / motilities and angiogenesis were massively affected by GIRK1 overexpression. Overexpression of different GIRK1 splice variants exerted differential actions. While GIRK1a and GIRK1c overexpression reinforced the affected parameters towards malignancy, overexpression of GIRK1d resulted in the opposite. Single channel recording using the patch clamp technique revealed functional GIRK channels in the plasma membrane of MCF-7 cells albeit at very low frequency.DiscussionWe conclude that GIRK1d acts as a dominant negative constituent of functional GIRK complexes present in the plasma membrane of MCF-7 cells, while overexpression of GIRK1a and GIRK1c augmented their activity. The core component responsible for the cancerogenic action of GIRK1 is apparently presented by a segment comprising aminoacids 235–402, that is present exclusively in GIRK1a and GIRK1c, but not GIRK1d (positions according to GIRK1a primary structure).ConclusionsThe current study provides insight into the cellular and molecular consequences of KCNJ3 overexpression in breast cancer cells and the mechanism upon clinical outcome in patients suffering from breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2664-8) contains supplementary material, which is available to authorized users.
Background: The use of transcranial laser or light-emitting diode (LED) therapy in the treatment of different neurological diseases is attracting increasing attention. The main goal of this study was to investigate different kinds of scientifically and commercially available laser (yellow, red, and infrared) and LED stimulation systems for the first time using a chick embryo model under a fixed human cadaver (scalp and/or skull) and without this anatomical preparation. Methods: In the present study, the extra-embryonic vasculature of a 1-week-old chick embryo chorioallantoic membrane (CAM) was investigated. For stimulation, four different systems were used (infrared LED and yellow, red, and infrared laser). Four measurement periods were compared: before stimulation, immediately after stimulation onset, immediately after the 10-min stimulation was turned off, and 6 min after stimulation had ended. Special image processing programs developed at the Beijing University of Science and Technology were used for data analysis. Results: The different kinds of laser induced different effects, e.g. the direct stimulation with yellow laser led to initial vasoconstriction (-17%), whereas yellow laser stimulation through a human skull resulted in an increase in blood volume. These effects could only be observed after mathematical processing of the images. Conclusion: After intensive basic research (e.g. CAM model), transcranial laser stimulation may open up new therapies for lifestyle-related diseases such as stroke, dementia, Alzheimer's or possibly Parkinson's disease.
Highlights d miR-181a promotes DC-SIGN expression during terminal mo-DC differentiation d miR-181a limits DC-SIGN + mo-DC responsiveness to inflammatory stimuli d miR-181a fine-tunes terminal mo-DC differentiation by modulating ERK-MAPK signaling
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