A5052708577- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Bone and Dental Protein Studies
- Adipokines, Inflammation, and Metabolic Diseases
- Cell Adhesion Molecules Research
- Adipose Tissue and Metabolism
- Lipoproteins and Cardiovascular Health
- Immune Response and Inflammation
- Vitamin D Research Studies
- Signaling Pathways in Disease
- Immunotherapy and Immune Responses
- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Computational Drug Discovery Methods
- Cytokine Signaling Pathways and Interactions
- Alzheimer's disease research and treatments
- Cancer-related gene regulation
- Atherosclerosis and Cardiovascular Diseases
- Neurological disorders and treatments
- Lipid Membrane Structure and Behavior
- NF-κB Signaling Pathways
- Mast cells and histamine
- Kruppel-like factors research
- PI3K/AKT/mTOR signaling in cancer
- Chronic Kidney Disease and Diabetes
AFFiRiS (Austria)
2014-2024
Intercell (Austria)
2005
University of Vienna
1997-2003
Medical University of Vienna
1999-2001
Institute of Immunology
2000-2001
Novartis (Austria)
2001
Austrian Institute for International Affairs
2001
Tamm-Horsfall glycoprotein (THP) is expressed exclusively in the kidney and constitutes most abundant protein mammalian urine. A critical role for THP antibacterial host defense inflammatory disorders of urogenital tract has been suggested. We demonstrate that activates myeloid DCs via Toll-like receptor-4 (TLR4) to acquire a fully mature DC phenotype. triggers typical TLR signaling, culminating activation NF-kappaB. Bone marrow-derived macrophages from TLR4- MyD88-deficient mice were...
Tamm-Horsfall glycoprotein (THP) is expressed exclusively in the kidney and constitutes most abundant protein mammalian urine. A critical role for THP antibacterial host defense inflammatory disorders of urogenital tract has been suggested. We demonstrate that activates myeloid DCs via Toll-like receptor-4 (TLR4) to acquire a fully mature DC phenotype. triggers typical TLR signaling, culminating activation NF-κB. Bone marrow–derived macrophages from TLR4- MyD88-deficient mice were...
Polyunsaturated fatty acids (PUFAs) suppress immune responses and inhibit T cell activation through largely unknown mechanisms. The displacement of signaling proteins from membrane lipid rafts has recently been suggested as underlying PUFA-mediated inhibition. We show here that PUFA treatment specifically interferes with signal transduction by blocking tyrosine phosphorylation LAT (linker for cells) phospholipase Cγ1. A significant fraction was displaced along other proteins. However,...
CD147 is a broadly expressed cell surface glycoprotein of the Ig superfamily whose expression up-regulated upon T activation. In order to elucidate possible role in biology, we established 15 specific mAb. Seven distinct epitopes were defined by mAb panel. Most bound only phytohemagglutinin (PHA)-activated but not resting cells. We demonstrate that this was because true activation-dependent neoepitopes rather due bivalent binding relatively low-affinity (affinity constant KA values between...
Recent findings point towards an important role of local macrophage proliferation also in obesity-induced adipose tissue inflammation that underlies insulin resistance and type 2 diabetes. Osteopontin (OPN) is inflammatory cytokine highly upregulated (AT) obese has repeatedly been shown to be functionally involved adipose-tissue metabolic sequelae. In the present work, we aimed at unveiling both OPN human monocyte as well impact deficiency on a mouse model for diet-induced obesity. The...
Abstract Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disease with limited symptomatic treatment options. Aggregation of α‐synuclein in oligodendrocytes believed to be central mechanism the process. PD01A PD03A are 2 novel therapeutic vaccine candidates containing short peptides as antigenic moieties that designed induce sustained antibody response, specifically targeting pathogenic assemblies α‐synuclein. The objectives current study were evaluate primarily safety...
Background: Immunotherapies targeting α-synuclein aim to limit its extracellular spread in the brain and prevent progression of pathology Parkinson’s disease (PD). PD03A is a specific active immunotherapy (SAIT) involving immunization with short peptide formulation. Objective: This phase 1 study characterized safety tolerability patients early PD. A key secondary objective was evaluate immunological activity following immunization. Methods: two different doses versus placebo PD patients....
Abstract Purpose AT04A and AT06A are two AFFITOPE® peptide vaccine candidates being developed for the treatment of hypercholesterolemia by inducing proprotein convertase subtilisin/kexin type 9 (PCSK9)-specific antibodies. This study aimed to investigate safety, tolerability, antibody development, reduction low-density lipoprotein cholesterol (LDLc) following four subcutaneous immunizations. Methods phase I, single-blind, randomized, placebo-controlled was conducted in a total 72 healthy...
CD93 is a approximately 120 kDa O-sialoglycoprotein that within the hematopoietic system selectively expressed on cells of myeloid lineage. So far, its primary structure and function were unknown. We used retroviral-expression cloning to isolate cDNA. Sequence analysis revealed identical protein human phagocytes termed C1q receptor (C1qRp). C1qRp was shown previously mediate enhancement phagocytosis in monocytes suggested be two other structurally related molecules. When studying...
The metabolic syndrome is becoming increasingly prevalent in the general population that at simultaneous risk for both type 2 diabetes and cardiovascular disease. critical pathogenic mechanisms underlying these diseases are obesity-driven insulin resistance atherosclerosis, respectively. To obtain a better understanding of molecular involved pathogenesis as basis future treatment strategies, studies considering inherent risks, namely cardiovascular, needed. Hence, aim this study was to...
Obesity and particularly the metabolic syndrome, which is often associated with obesity, combine a major risk for type 2 diabetes cardiovascular disease. Emerging evidence indicate obesity-associated subclinical inflammation primarily originating from adipose tissue as common cause However, suitable well-characterized mouse model to simultaneously study disorders atherosclerosis not available yet. Here we established characterized murine combining diet-induced obesity deteriorations well...
Objective Macrophages are the main drivers of obesity‐induced adipose tissue (AT) inflammation that causes insulin resistance. polarize toward different inflammatory (M1) or protective (M2) phenotypes. Osteopontin (OPN) is an cytokine highly expressed in AT obesity and known to be involved chronic processes. It was hypothesized OPN polarizes macrophages into a proinflammatory phenotype. Methods (ATMs) OPN‐deficient ( Spp1 −/− ) wild‐type C57BL/6 (WT) mice with bone marrow‐derived (BMDMs) WT...
Abstract The plasma membrane is compartmentalized into microdomains and the association/dissociation of receptors signaling molecules with/from these domains a major principle for regulation signal transduction. By following reorganization on living cells performing biochemical studies, we show that Ab targeting T cell activation-associated Ag CD147 prevents TCR stimulation-dependent clustering microdomains. Triggering induces displacement GPI-anchored coreceptors CD48 CD59 from in human...
Abstract Human CD1 form a group of nonpolymorphic leukocyte surface molecules with homology to major histocompatibility complex (MHC) proteins. Recent findings in human and mouse demonstrate the capacity present nonpeptide components like lipids or lipoglycans as well peptides. We studied involvement β2‐microglobulin (β2m) expression classic proteins CD1a, CD1b, CD1c. The β2m‐deficient melanoma cell line FO‐1 was transiently transfected either CD1c DNA alone, combination β2m using...
Abstract CDw92 is a 70-kDa surface protein broadly expressed on leukocytes and endothelial cells. In this manuscript, we present the molecular cloning of molecule by using highly efficient retroviral expression system. Sequence analysis cDNA revealed length 2679 bp. The 1959-bp open reading frame encodes 652 amino acids. Computational sequence indicates 10 transmembrane domains, three potential N-linked glycosylation sites, an acid stretch in C-terminal region that related to immunoreceptor...
beta(2)-Microglobulin (beta(2)m)-associated human CD1b proteins present lipid and glycolipid antigens, which are loaded on in endosomal compartments. In contrast, the related MHC class I molecules acquire antigenic peptides endoplasmic reticulum. Here, we investigated biogenesis of before beta(2)m binding comparison to I. beta(2)m-deficient FO-1 cells, found heavy chains (HC) complexed with chaperones calnexin calreticulin, while HC associated only calnexin. Despite this difference, both...
Abstract CD31 is a member of the Ig superfamily expressed on various cell types vasculature, including certain subpopulation T lymphocytes. Previous reports suggest that interaction with its heterophilic ligand cells (T ligand) plays regulatory role in lymphocyte activation. Here we demonstrate soluble rCD31-receptorglobulin (CD31Rg) specifically down-regulated proliferation human peripheral blood CD31− lymphocytes stimulated via CD3 and CD28 mAbs. Notably, engagement by CD31Rg during...
Osteopontin (OPN) is upregulated in adipose tissue (AT) obesity and contributes to subclinical inflammation, adipocyte dysfunction, insulin resistance. OPN effects can be increased by cleavage matrix metalloproteinases (MMP). This study aimed at investigating the presence of products human AT their impact on function immunological blockade these effects. severely obese control donors was investigated for MMP expression fragments. Primary adipocytes were isolated from vitro investigation...
<b>Background:</b> In vivo, all blood vessels are lined by a single layer of flattened noncycling endothelial cells. We tested the hypothesis that maintenance such quiescent monolayer depends on homotypic contacts between not yet defined growth–inhibitory molecules located at interendothelial junctions. <b>Methods:</b> ECV304 cells, which lack endogenous vascular cadherin (VE cadherin) or CD31 expression, were transfected with cDNA encoding for respective proteins...
Osteopontin (OPN), a secreted protein involved in inflammatory processes and cancer, induces cell adhesion, migration, activation of pathways various types. Cells bind OPN via integrins at canonical RGD region the full length form as well to contiguous cryptic site that some have shown is unmasked upon thrombin or matrix metalloproteinase cleavage. Thus, adhesive capacity osteopontin enhanced by proteolytic cleavage may occur conditions such obesity, atherosclerosis, rheumatoid arthritis,...
Background. Tyrphostin AG490 has recently been shown to block interleukin (IL)-2 receptor γ-chain-associated Janus kinase 3. Here, we analyzed the effect of on T-cell alloresponses in vitro. Methods. For evaluation activation, DNA synthesis, surface marker expression, cytokine secretion, intracellular calcium mobilization, early protein tyrosine phosphorylation, and apoptosis were measured. Results. effectively inhibited proliferation human mixed lymphocyte culture (MLC) even when added 4...