A5090211379- Rheumatoid Arthritis Research and Therapies
- Cytokine Signaling Pathways and Interactions
- Systemic Lupus Erythematosus Research
- Spondyloarthritis Studies and Treatments
- NF-κB Signaling Pathways
- Cell Adhesion Molecules Research
- interferon and immune responses
- Inflammatory Bowel Disease
- Spine and Intervertebral Disc Pathology
- Cancer-related molecular mechanisms research
- Immune cells in cancer
- Hepatitis B Virus Studies
- Immune Response and Inflammation
- Bone Metabolism and Diseases
- Cancer Cells and Metastasis
- Circular RNAs in diseases
- RNA modifications and cancer
- HER2/EGFR in Cancer Research
- Osteoarthritis Treatment and Mechanisms
- MicroRNA in disease regulation
- Inflammatory mediators and NSAID effects
- IL-33, ST2, and ILC Pathways
- Cell death mechanisms and regulation
- Signaling Pathways in Disease
- Inflammasome and immune disorders
Alexander Fleming Biomedical Sciences Research Center
2015-2024
National and Kapodistrian University of Athens
2020
Institute of Immunology
2019
Case Western Reserve University
2011
Aristotle University of Thessaloniki
1999
Valvular heart disease affects 1%–2% of young individuals, many whom aspire to partake in competitive sport or high intensity recreational exercise. There are limited reports on the impact intensive physical activity progression valvular disease; therefore, current recommendations based consensus opinion. The management exercising individuals with requires a structured approach that incorporates several key factors including symptomatic status, functional capacity, type and nature lesion,...
Tumor necrosis factor (TNF) is key to the pathogenesis of various arthritic diseases and inflammatory bowel disease (IBD). Anti-TNF therapies have proved successful in clinical treatment these diseases, but a mechanistic understanding TNF function still lacking. We investigated early cellular mechanisms using an established transgenic model, which develops spondyloarthritis-like characterized by peripheral joint arthritis, sacroiliitis, enthesitis, Crohn's-like IBD. Bone marrow grafting...
Objective RANKL is mainly expressed by synovial fibroblasts and T cells within the joints of rheumatoid arthritis patients. The relative importance expression these cell types for formation bone erosions unclear. We therefore aimed to quantify contribution each type osteoclast differentiation destruction during inflammatory arthritis. Methods was specifically deleted in ( Tnfsf11 flox/Δ Lck -Cre), collagen VI expressing including Col6a1 -Cre) II articular chondrocytes Col2a1 -Cre). Erosive...
Recent clinical evidence demonstrated the importance of tumor necrosis factor (TNF) in development Crohn's disease. A mouse model for this pathology has previously been established by engineering defects translational control TNF mRNA (TnfΔAREmouse). Here, we show that intestinal depends on Th1-like cytokines such as interleukin 12 and interferon γ requires function CD8+ T lymphocytes. Tissue-specific activation mutant allele Cre/loxP-mediated recombination indicated either myeloid- or...
p38 mitogen-activated protein kinases (MAPKs) are activated primarily in response to inflammatory cytokines and cellular stress, inhibitors which target the p38alpha p38beta MAPKs have shown potential for treatment of disease. Here we report generation initial characterization a knockout (MAPK11) gene. p38beta-/- mice were viable exhibited no apparent health problems. The expression activation p38alpha, ERK1/2, JNK stress was normal embryonic fibroblasts from mice, as p38-activated MAPKAP-K2...
Rheumatoid arthritis is a destructive arthropathy characterized by chronic synovial inflammation that imposes substantial socioeconomic burden. Under the influence of proinflammatory milieu, fibroblasts (SFs), main effector cells in disease pathogenesis, become activated and hyperplastic, releasing factors tissue-remodeling enzymes. This study shows arthritic SFs from human patients animal models express significant quantities autotaxin (ATX; ENPP2), lysophospholipase D catalyzes conversion...
A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences synovial fibroblasts from different joint locations that HOX gene signatures reflect the joint-specific origins mouse tissues. Alongside DNA methylation histone modifications, bromodomain extra-terminal reader proteins regulate expression. Anatomical transcriptional diversity translates into fibroblast phenotypes with...
TNF plays a crucial role in the pathogenesis of Crohn disease. Dysregulated production mice that bear genetic deletion AU-rich regulatory elements (ARE) ( Tnf ΔARE/+ mice) results receptor I (TNFRI)-dependent spontaneous Crohn-like pathology. Current concepts consider intestinal epithelial cell (IEC) responses to be critical for pathology, but potential contribution IEC-derived disease has not been addressed. In this study we examined whether IEC are sufficient as cellular targets or sources...
Animal models for inflammatory arthritides such as rheumatoid arthritis (RA) and psoriatic are widely accepted frequently used to identify pathological mechanisms validate novel therapeutic strategies. Unfortunately, many publications reporting on these animal studies lack detailed description appropriate assessment of the distinct histopathological features arthritis: joint inflammation, cartilage damage bone erosion. Therefore, European consortium BeTheCure, consisting 38 academic...
Synovial fibroblasts (SFs) are specialized cells of the synovium that provide nutrients and lubricants for proper function diarthrodial joints. Recent evidence appreciates contribution SF heterogeneity in arthritic pathologies. However, normal profiles molecular networks govern transition from homeostatic to remain poorly defined.
TNF has remarkable antitumor activities; however, therapeutic applications have not been possible because of the systemic and lethal proinflammatory effects induced by TNF. Both inflammatory are mediated receptor p55 (p55TNFR) (encoded Tnfrsf1a gene). The effect stems from an induction cell death in tumor endothelium, but type that initiates cascade unclear. Using conditional knockout or reactivation mice, we found expression level p55TNFR intestinal epithelial cells (IECs) is a crucial...
Lung cancer and chronic lung diseases impose major disease burdens worldwide are caused by inhaled noxious agents including tobacco smoke. The cellular origins of environmental-induced tumors the dysfunctional airway alveolar epithelial turnover observed with unknown. To address this, we combined mouse models genetic labeling ablation (club) cells exposure to environmental carcinogenic agents. Club shown survive KRAS mutations form after carcinogen exposure. Increasing numbers club found in...
Abstract Although patients with rheumatoid arthritis (RA) typically exhibit symmetrical joint involvement, some develop alternative disease patterns in response to treatment, suggesting that different molecular mechanism may underlie progression depending on location. Here, we identify joint-specific changes RA synovium and synovial fibroblasts (SF) between knee hand joints. We show the long non-coding RNA HOTAIR, which is only expressed SF, regulates more than 50% of this site-specific gene...
Abstract NFκB activation and regulated cell death are important in tissue homeostasis, inflammation pathogenesis. Here we show the role of p55TNFR–IKK2l–Ripk3 axis regulation synovial fibroblast homeostasis pathogenesis TNF-mediated mouse models arthritis. Mesenchymal-specific p55TNFR triggering is indispensable for arthritis acute chronic TNF-dependent models. IKK2 joint mesenchymal cells necessary development cartilage destruction bone erosion; however, its absence synovitis still...
Abstract TNF-α, a potent proinflammatory cytokine, is generated in precursor form called transmembrane (m)TNF-α that expressed as type II polypeptide on the surface of certain cells. mTNF-α was shown to act both ligand by binding TNF-α receptors, well receptor transmits outside-to-inside (reverse) signals back into mTNF-α–bearing In this study, we show nonactivated macrophages express basal levels and respond anti–TNF-α Abs triggering MAPK kinase 4 signaling pathway. The pathway induces...
TNF plays a key role in immune-mediated inflammatory diseases including rheumatoid arthritis (RA) and spondyloarthritis (SpA). It remains incompletely understood how can lead to different disease phenotypes such as destructive peripheral polysynovitis RA versus axial osteoproliferative inflammation SpA. We observed marked increase of transmembrane (tm) soluble (s) SpA together with decrease the enzymatic activity ADAM17. In contrast classical overexpression models, mice overexpressing tmTNF...
Rheumatoid arthritis is a chronic inflammatory disease with high prevalence and substantial socioeconomic burden. Despite intense research efforts, its aetiology pathogenesis remain poorly understood. To identify novel genes and/or cellular pathways involved in the of disease, we utilized well-recognized tumour necrosis factor-driven animal model this performed high-throughput expression profiling subtractive cDNA libraries oligonucleotide microarray hybridizations, coupled independent...