Search results for "ACTIVATOR"
showing 10 items of 488 documents
Role of β1H for the binding of C3b-coated particles to human lymphoid and phagocytic cells
1981
Coating of EAC14oxy23b with highly purified human serum beta 1H globulin (beta 1H) led to acceleration of rosette formation with human peripheral blood lymphocytes (PBL), tonsil lymphocytes, B lymphoblastoid (Raji) cells, granulocytes and monocytes. This reaction was discernible from C3bi-dependent rosette formation. Enhancement of rosette formation of C3b cells by beta 1H was most effective at limiting amounts of C3 per EAC14oxy23b. The beta 1H effect was not due to trace contamination with C3b inactivator. beta 1H-dependent rosette formation with the various lymphoid and phagocytic cells could be suppressed by the F(ab')2 fragment of anti-beta 1H suggesting beta 1H-mediated binding of bet…
Comparison of a Novel Homogeneous Cyclic Amp Assay and a Luciferase Assay for Measuring Stimulating Thyrotropin-Receptor Autoantibodies.
2019
Objective: Stimulating thyrotropin-receptor antibodies (TSAb) cause Graves’ disease (GD). We tested a novel homogeneous fluorescent 3′,5′ cyclic adenine monophosphate (cAMP) assay for the detection of TSAb in a bioassay. Methods: Chinese hamster ovary (CHO) cell lines expressing either a chimeric (MC4) or wild-type (WT) TSH-R were incubated with the adenyl cyclase activator forskolin, a human TSAb monoclonal antibody (M22), and with sera from GD patients. Intracellular cAMP levels were measured using a Bridge-It® cAMP assay, and the results were compared with a luciferase-based bioassay. Results: Both cell lines were stimulated with forskolin concentrations (0.006–200 µM) in a dose-dependen…
Urokinase Plasminogen Activator and Gelatinases Are Associated with Membrane Vesicles Shed by Human HT1080 Fibrosarcoma Cells
1997
Membrane vesicles are shed by tumor cells both in vivo and in vitro. Although their functions are not well understood, it has been proposed that they may play multiple roles in tumor progression. We characterized membrane vesicles from human HT1080 fibrosarcoma cell cultures for the presence of proteinases involved in tumor invasion. By gelatin zymography and Western blotting, these vesicles showed major bands corresponding to the zymogen and active forms of gelatinase B (MMP-9) and gelatinase A (MMP-2) and to the MMP-9. tissue inhibitor of metalloproteinase 1 complex. Both gelatinases appeared to be associated with the vesicle membrane. HT1080 cell vesicles also showed a strong, plasminoge…
Homologies Between Different Forms of 2-5A Synthetases
1994
(2′-5′) Oligoadenylate synthetases (2-5A synthetases; EC 2.7.7.19) are present in mammalian cells and tissues and synthesize from ATP a series of oligomers termed 2-5A [general formula: ppp(A2′p)nA; with 1 ≤ n < 18 and usually 1 ≤ n < 6] (Hovanessian 1991). For full enzymic activity of the 2-5A synthetases, binding of double-stranded RNA is required (Sen 1982). Three principal 2-5A synthetase isoenzymes have been described with Mr’s of 40–46, 69, and 100 kDa (Chebath et al. 1987; Hovanessian et al. 1987, 1988). In the following they are classified as 2-5A synthetase I [Mr 40–46 000], II [Mr 69 000] and III [Mr 100 000]. All three isoforms are induced in cells by interferon (Cohen et al. 198…
Sumoylation of the transcription factor NFATc1 leads to its subnuclear relocalization and interleukin-2 repression by histone deacetylase.
2009
The family of NFAT (nuclear factor of activated T-cells) transcription factors plays an important role in cytokine gene regulation. In peripheral T-cells NFATc1 and -c2 are predominantly expressed. Because of different promoter and poly(A) site usage as well as alternative splicing events, NFATc1 is synthesized in multiple isoforms. The highly inducible NFATc1/A contains a relatively short C terminus, whereas the longer, constitutively expressed isoform NFATc1/C spans an extra C-terminal peptide of 246 amino acids. Interestingly, this NFATc1/C-specific terminus can be highly sumoylated. Upon sumoylation, NFATc1/C, but not the unsumoylated NFATc1/A, translocates to promyelocytic leukemia nuc…
Targeting the JAK/STAT Pathway: A Combined Ligand- and Target-Based Approach
2021
Janus kinases (JAKs) are a family of proinflammatory enzymes able to mediate the immune responses and the inflammatory cascade by modulating multiple cytokine expressions as well as various growth factors. In the present study, the inhibition of the JAK-signal transducer and activator of transcription (STAT) signaling pathway is explored as a potential strategy for treating autoimmune and inflammatory disorders. A computationally driven approach aimed at identifying novel JAK inhibitors based on molecular topology, docking, and molecular dynamics simulations was carried out. For the best candidates selected, the inhibitory activity against JAK2 was evaluated in vitro. Two hit compounds with…
Gene Therapy in Rare Respiratory Diseases: What Have We Learned So Far?
2020
Gene therapy is an alternative therapy in many respiratory diseases with genetic origin and currently without curative treatment. After five decades of progress, many different vectors and gene editing tools for genetic engineering are now available. However, we are still a long way from achieving a safe and efficient approach to gene therapy application in clinical practice. Here, we review three of the most common rare respiratory conditions—cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), and primary ciliary dyskinesia (PCD)—alongside attempts to develop genetic treatment for these diseases. Since the 1990s, gene augmentation therapy has been applied in multiple clinical tria…
Overexpression of bone morphogenetic protein-6 (BMP-6) in murine epidermis suppresses skin tumor formation by induction of apoptosis and downregulati…
2001
Bone morphogenetic protein-6 (BMP-6) is a member of the transforming growth factor-beta superfamily. In murine skin, BMP-6 is highly expressed in postmitotic keratinocytes from day 15.5 p.c. till day 6 p.p. Expression in adult skin remains at very low levels, but pathological conditions such as wounding induce the expression of BMP-6. We demonstrate that tumor promotion by TPA (12-O-tetradecanoylphorbol-13-acetate) also induces expression of BMP-6 in suprabasal keratinocytes. This induction is due to post-transcriptional regulation since the level of BMP-6 mRNA remained unchanged. We performed two-stage skin carcinogenesis experiments with transgenic mice epidermally overexpressing BMP-6. T…
Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression.
2001
Recent studies in transgenic mice have revealed that expression of a dominant negative form of the transcription factor GATA-3 in T cells can prevent T helper cell type 2 (Th2)-mediated allergic airway inflammation in mice. However, it remains unclear whether GATA-3 plays a role in the effector phase of allergic airway inflammation and whether antagonizing the expression and/or function of GATA-3 can be used for the therapy of allergic airway inflammation and hyperresponsiveness. Here, we analyzed the effects of locally antagonizing GATA-3 function in a murine model of asthma. We could suppress GATA-3 expression in interleukin (IL)-4–producing T cells in vitro and in vivo by an antisense ph…
TGF-β Suppresses Tumor Progression in Colon Cancer by Inhibition of IL-6 trans-Signaling
2004
Alterations of TGF-beta signaling have been described in colorectal cancer, although the molecular consequences are largely unknown. By using transgenic mice overexpressing TGF-beta or a dominant-negative TGF-betaRII, we demonstrate that TGF-beta signaling in tumor infiltrating T lymphocytes controls the growth of dysplastic epithelial cells in experimental colorectal cancer, as determined by histology and a novel system for high-resolution chromoendoscopy. At the molecular level, TGF-beta signaling in T cells regulated STAT-3 activation in tumor cells via IL-6. IL-6 signaling required tumor cell-derived soluble IL-6R rather than membrane bound IL-6R and suppression of such TGF-beta-depende…