Search results for "RECEPTORS"
showing 10 items of 3254 documents
Targeting of biotinylated compounds to its target tissue using a low-density lipoprotein receptor–avidin fusion protein
2003
The very high binding affinity of avidin to biotin is one of the highest to occur in nature. We constructed a fusion protein composed of avidin and the endocytotic LDL receptor in order to target biotinylated molecules to cells of the desired tissues. In addition to the native avidin, charge-mutated and nonglycosylated avidins were utilized as part of the fusion proteins, in order to modify its properties. All of the fusion protein versions retained the biotin-binding capacity. Although the specificity was not increased, however, fusion proteins composed of natural avidin and nonglycosylated avidin bound most efficiently to the biotinylated ligands. Fluorescence microscopy and atomic force …
SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells
2012
Abstract SAHA, an inhibitor of histone deacetylase activity, has been shown to sensitize tumor cells to apoptosis induced by TRAIL, a member of TNF-family. In this paper we investigated the effect of SAHA/TRAIL combination in two breast cancer cell lines, the ERα−positive MCF-7 and the ERα−negative MDA-MB231. Treatment of MDA-MB231 and MCF-7 cells with SAHA in combination with TRAIL caused detachment of cells followed by anoikis, a form of apoptosis which occurs after cell detachment, while treatment with SAHA or TRAIL alone did not produce these effects. The effects were more evident in MDA-MB231 cells, which were chosen for ascertaining the mechanism of SAHA/TRAIL action. Our results show…
Role of interleukin-6 and soluble IL-6 receptor in region-specific induction of astrocytic differentiation and neurotrophin expression.
1999
Increasing evidence supports an essential role for interleukin-6 (IL-6) in the development, differentiation, as well as de- and re-generation of neurons in the central nervous system (CNS). Both IL-6 and its specific receptor (IL-6R) are expressed on neurons and glial cells including astrocytes. In this study, we have analyzed the responses of primary rat astrocytes of various brain regions to IL-6 with respect to morphological changes and neurotrophin expression. Since IL-6 alone failed to initiate effects on astrocytes, we have examined whether the soluble IL-6R (sIL-6R) can modulate the responsiveness of to IL-6 in these cells. For this purpose, we used a highly active fusion protein of …
Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27
2006
The immune response to bacterial infections must be tightly controlled to guarantee pathogen elimination while preventing tissue damage by uncontrolled inflammation. Here, we demonstrate a key role of interleukin (IL)-27 in regulating this critical balance. IL-27 was rapidly induced during murine experimental peritonitis induced by cecal ligation and puncture (CLP). Furthermore, mice deficient for the EBI3 subunit of IL-27 were resistant to CLP-induced septic peritonitis as compared with wild-type controls, and this effect could be suppressed by injection of recombinant single-chain IL-27. EBI3−/− mice displayed significantly enhanced neutrophil migration and oxidative burst capacity during…
Soluble interleukin-6 receptor (sIL-6R) makes IL-6R negative T cell line respond to IL-6: it inhibits TNF production
2000
The receptor for interleukin-6 (IL-6) consists of two subunits: a ligand specific IL-6Ralpha and gp130 that is responsible for signal-transduction. A soluble form of the ligand specific chain was described that when complexed to IL-6 is capable of binding to the membrane-bound gp130 subunit and thus can elicit signal-transduction. This soluble receptor can act on cells that express only the gp130 but not the ligand-specific subunit of the IL-6R. This phenomenon, called trans-signaling, introduced a novel aspect of cytokine action. In this study we examined the response of Jurkat cells, that are known not to express IL-6Ralpha, to IL-6, the soluble IL-6 receptor (sIL-6R) and a covalent compl…
Non-Classical Transformation of Benzendiazonium Hydrogen Sulfates. Access to 1,3-Dimethylisochromeno[4,3-c]pyrazol-5(1H)-one, a Potential Benzodiazep…
2013
The compound 2-((1,3-dimethyl-1H-pyrazol-5-yl)(methyl)carbamoyl)benzene-diazonium hydrogen sulfate (10) was reacted with copper sulfate and sodium chloride, in the presence of ascorbic acid as reducing agent, to afford a mixture of the chlorinated epimers 4′-chloro-2,2′,5′-trimethyl-2′,4′-dihydrospiro[isoindoline-1,3′-pyrazol]-3-one (18) and (19), the epimers 4′-hydroxy-2,2′,5′-trimethyl-2′,4′-dihydrospiro[isoindoline-1,3′-pyrazol]-3-one (20) and (21), and N-(1,3-dimethyl-1H-pyrazol-5-yl)benzamide (22). Under the foregoing conditions, diazonium salt 10 affords neither the 2-chloro-N-(1,3-dimethyl-1H-pyrazol-5-yl)-N-methylbenzamide (23) nor the tricyclic derivative 24, the classical products…
Purinergic receptors influence the differentiation of human mesenchymal stem cells
2011
Adult stem cells, including adipose tissue-derived mesenchymal stem cells (MSCs) or ectomesenchymal dental follicle cells (DFCs), attract considerable attention for their potential to differentiate into lineages, which are of major interest in the field of Regenerative Medicine. Purinergic receptors exert a wide range of biological actions in many cell and tissue types through extracellular nucleotides. Little is known about P2 receptors in adult stem cells and changes in their expression levels during differentiation. All known P2 receptors have been investigated, and a variety of P2X and P2Y receptor subtypes were detected in MSCs. Studies investigating intracellular calcium levels on rec…
Toll-like receptors and autoimmunity
2008
The understanding of autoimmune diseases experienced an impressive boost since the Toll-like receptors (TLRs) have been identified as possible key players in autoimmune pathophysiology. Although these receptors recognize a variety of structures derived from viruses, bacteria and fungi leading to subsequent initiation of the relevant immune responses recent data support the idea that TLRs are crucial in the induction and perpetuation of certain autoimmune diseases, especially the systemic lupus erythematosus (SLE). In this review we will summarize recent data on involvement of TLRs in the development of autoimmune diseases. This review will focus on TLRs 7, 8 and 9 which were originally iden…
Cutting Edge: Trans-Signaling via the Soluble IL-6R Abrogates the Induction of FoxP3 in Naive CD4+CD25− T Cells
2007
Abstract Chronic inflammatory diseases may develop when regulatory T cells (Tregs) fail to control the balance between tolerance and immunity. Alternatively, activated immune cells might prevent the induction or activation of Tregs in such diseases. In this study, we demonstrate that trans-signaling into T cells via the soluble IL-6 receptor completely abrogates the de novo induction of adaptive Tregs. Mechanistically, IL-6 trans-signaling augmented the expression of the TGF-β signaling inhibitor SMAD7. Consequently, SMAD7 overexpression in T cells using newly created transgenic mice rendered CD4+CD25− T cells resistant to the induction of FoxP3. Finally, IL-6 trans-signaling inhibited Treg…
Tumor cells convert immature myeloid dendritic cells into TGF-β–secreting cells inducing CD4+CD25+ regulatory T cell proliferation
2005
The mechanisms through which regulatory T cells accumulate in lymphoid organs of tumor-bearing hosts remain elusive. Our experiments indicate that the accumulation of CD4+CD25+ regulatory T cells (T reg cells) expressing FoxP3 and exhibiting immunosuppressive function originates from the proliferation of naturally occurring CD25+ T cells and requires signaling through transforming growth factor (TGF)–β receptor II. During tumor progression, a subset of dendritic cells (DCs) exhibiting a myeloid immature phenotype is recruited to draining lymph nodes. This DC subset selectively promotes the proliferation of T reg cells in a TGF-β–dependent manner in mice and rats. Tumor cells are necessary a…