Search results for "alpha Subunit"
showing 10 items of 126 documents
Differential response of neuronal cells to a fusion protein of ciliary neurotrophic factor/soluble CNTF-receptor and leukemia inhibitory factor
2002
Ciliary neurotrophic factor (CNTF) displays neurotrophic activities on motor neurons and neural cell populations both in vivo and in vitro. On target cells lacking intrinsic expression of specific receptor alpha subunits cytokines of the IL-6 family only act in the presence of their specific agonistic soluble receptors. Here, we report the construction and expression of a CNTF/soluble CNTF-receptor (sCNTF-R) fusion protein (Hyper-CNTF) with enhanced biological activity on cells expressing gp130 and leukemia inhibitory factor receptor (LIF-R), but not membrane-bound CNTF-R. At the cDNA level, the C-terminus of the extracellular domain of human CNTF-R (amino acids 1-346) was linked via a sing…
Crosstalk of regulatory T cells and tolerogenic dendritic cells prevents contact allergy in subjects with low zone tolerance
2012
Background Allergic contact dermatitis is one of the most common occupational diseases. A main protective mechanism in those who do not develop allergic contact dermatitis is tolerance induction by repeated exposure to low doses of contact allergen, which is termed low zone tolerance (LZT). The mechanisms that determine the tolerance induction in subjects with LZT are still elusive. Objective We performed analysis of the role of CD4 + CD25 + forkhead box protein 3 (FOXP3)–positive regulatory T (Treg) cells and dendritic cells (DCs) in mice with LZT. Methods Mechanisms of tolerance induction were analyzed in a murine model of LZT by using FOXP3 and IL-10 reporter mice, as well as mice that a…
Functional regulation of HIF-1α under normoxia--is there more than post-translational regulation?
2011
The hypoxia-inducible factor-1 (HIF-1) is an oxygen-regulated transcriptional activator playing a pivotal role in mammalian physiology and disease pathogenesis, e.g., HIF-1 is indispensable in a broad range of developmental stages in different tumors. Its post-translational regulation via PHDs under the influence of hypoxia is widely investigated and accepted. Different non-hypoxic stimuli such as lipopolysaccharides (LPS), thrombin, and angiotensin II (Ang II), have been proven to enhance HIF-1 levels through activation of regulative mechanisms distinct from protein stabilization. Some of these stimuli specifically regulate HIF-1α at the transcriptional, post-transcriptional, or translatio…
Large scale preparation of human MHC class II+ integrin beta(1)+ Tregs.
2010
Abstract The human CD4 + CD25 + FoxP3 + regulatory T cell population (Tregs) contains both MHC class II + and MHC class II − cells. MHC class II + Tregs belong to the integrin α 4 β 1 + subpopulation and exclusively execute contact-dependent suppressive activity. Here we present a method optimized for isolation of these MHC class II expressing Tregs from large leukaphereses products using magnetic microbeads that achieves a reproducible purity of more than 90% and enables the use of this small-sized Treg population in pre-clinical application and basic research.
Short-Time Ocular Ischemia Induces Vascular Endothelial Dysfunction and Ganglion Cell Loss in the Pig Retina
2019
Visual impairment and blindness are often caused by retinal ischemia-reperfusion (I/R) injury. We aimed to characterize a new model of I/R in pigs, in which the intraocular pathways were not manipulated by invasive methods on the ocular system. After 12 min of ischemia followed by 20 h of reperfusion, reactivity of retinal arterioles was measured in vitro by video microscopy. Dihydroethidium (DHE) staining, qPCR, immunohistochemistry, quantification of neurons in the retinal ganglion cell layer, and histological examination was performed. Retinal arterioles of I/R-treated pigs displayed marked attenuation in response to the endothelium-dependent vasodilator, bradykinin, compared to sham-tre…
Inhibition of VEGF expression through blockade of Hif1a and STAT3 signalling mediates the anti-angiogenic effect of melatonin in HepG2 liver cancer c…
2013
Background: Hepatocellular carcinoma (HCC) growth relies on angiogenesis via vascular endothelial growth factor (VEGF) release. Hypoxia within tumour environment leads to intracellular stabilisation of hypoxia inducible factor 1 alpha (Hif1α) and signal transducer and activator of transcription (STAT3). Melatonin induces apoptosis in HCC, and shows anti-angiogenic features in several tumours. In this study, we used human HepG2 liver cancer cells as an in vitro model to investigate the anti-angiogenic effects of melatonin. Methods: HepG2 cells were treated with melatonin under normoxic or CoCl2-induced hypoxia. Gene expression was analysed by RT–qPCR and western blot. Melatonin-induced anti-…
miR-20b modulates VEGF expression by targeting HIF-1 alpha and STAT3 in MCF-7 breast cancer cells.
2010
MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of different genes, including genes involved in cancer progression. A functional link between hypoxia, a key feature of the tumor microenvironment, and miRNA expression has been documented. We investigated whether and how miR-20b can regulate the expression of vascular endothelial growth factor (VEGF) in MCF-7 breast cancer cells under normoxic and hypoxia-mimicking conditions (CoCl(2) exposure). Using immunoblotting, ELISA, and quantitative real-time PCR, we demonstrated that miR-20b decreased VEGF protein levels at 4 and 24 h following CoCl(2) treatment, and VEGF mRNA at 4 h of treatment. In addition, miR-20b reduce…
Cholesterol Starvation and Hypoxia Activate the FVII Gene via the SREBP1-GILZ Pathway in Ovarian Cancer Cells to Produce Procoagulant Microvesicles
2019
AbstractInteraction between the transcription factors, hypoxia-inducible factor (HIF1α and HIF2α) and Sp1, mediates hypoxia-driven expression of FVII gene encoding coagulation factor VII (fVII) in ovarian clear cell carcinoma (CCC) cells. This mechanism is synergistically enhanced in response to serum starvation, a condition possibly associated with tumor hypoxia. This transcriptional response potentially results in venous thromboembolism, a common complication in cancer patients by producing procoagulant extracellular vesicles (EVs). However, which deficient serum factors are responsible for this characteristic transcriptional mechanism is unknown. Here, we report that cholesterol deficien…
Long Non Coding RNA H19: A New Player in Hypoxia-Induced Multiple Myeloma Cell Dissemination
2019
The long non-coding RNA H19 (lncH19) is broadly transcribed in the first stage of development and silenced in most cells of an adult organism
Nickel induces intracellular calcium mobilization and pathophysiological responses in human cultured airway epithelial cells.
2009
Abstract Environmental exposure to nickel is associated to respiratory disorders and potential toxicity in the lung but molecular mechanisms remain incompletely explored. The extracellular Ca 2+ -sensing receptor (CaSR) is widely distributed and may be activated by divalent cations. In this study, we investigated the presence of CaSR in human cultured airway epithelial cells and its activation by nickel. Nickel transiently increased intracellular calcium (−log EC 50 = 4.67 ± 0.06) in A549 and human bronchial epithelial cells as measured by epifluorescence microscopy. Nickel (20 μM)-induced calcium responses were reduced after thapsigargin or ryanodine exposure but not by Ca 2+ -free medium…