Search results for "RECEPTORS"

Synthetic retinoids dissociate coactivator binding from corepressor release.

2002

The ligand-activated retinoid receptors RXR and RAR control development, homeostasis and disease by regulating transcription of retinoic acid (RA) responsive target genes or crosstalk with other signalling pathways. According to the current model ligand-binding triggers an exchange between corepressor- and coactivator-complexes that inhibit or potentiate transcription by deacetylating and acetylating nucleosomal histones, respectively. Additional cofactors may modify the transcriptional regulatory process by linking liganded retinoid receptors to structural components of chromatin or protein degradation. The desire to specifically influence defined events in RA-signalling, while others are …

Interactions between cholinergic and fibroblast growth factor receptors in brain trophism and plasticity

2014

Acetylcholine, acting on both nicotinic receptors (nAChRs) and muscarinic receptors (mAChRs), plays a role in the regulation of synaptic plasticity, being involved in the regulation of cellular processes and cognitive functions, such as learning, memory and attention. Recently, G protein coupled receptors (GPCRs), including mAChRs, have been reported to transactivate tyrosine-kinase receptors (RTK), such as epidermal growth factor receptor (EGFR), and initiate their intracellular signaling. In this minireview we have first analysed the RTK transactivation mechanisms, involving cholinergic receptors, and thereafter the interplay between AChR and neurotrophic factor systems built up by FGF2 a…

Histamine Upregulates Gene Expression of Endothelial Nitric Oxide Synthase in Human Vascular Endothelial Cells

2003

Background— Histamine has a short-term, transient, stimulating effect on endothelial nitric oxide synthase (eNOS) activity; however, long-term effects on eNOS have not been described yet. In addition, the vascular effect of histamine seems to depend critically on eNOS functionality. Therefore, we studied the effects of histamine on eNOS gene expression and function. Methods and Results— In human umbilical vein endothelial cells (HUVECs) and HUVEC-derived EA.hy 926 cells, histamine upregulated eNOS mRNA (RNase protection assay) and protein (electron microscopic immunocytochemistry) expression. The upregulation of eNOS could be prevented by mepyramine, a selective antagonist at the H 1 recep…

In vivo manipulation of Vgamma9Vdelta2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients.

2010

The potent anti-tumour activities of gamma delta T cells have prompted the development of protocols in which gamma delta-agonists are administered to cancer patients. Encouraging results from small Phase I trials have fuelled efforts to characterize more clearly the application of this approach to unmet clinical needs such as metastatic carcinoma. To examine this approach in breast cancer, a Phase I trial was conducted in which zoledronate, a V gamma 9V delta 2 T cell agonist, plus low-dose interleukin (IL)-2 were administered to 10 therapeutically terminal, advanced metastatic breast cancer patients. Treatment was well tolerated and promoted the effector maturation of V gamma 9V delta 2 T …

CC chemokine receptor 5Δ32 polymorphism-a risk factor for ischemic-type biliary lesions following orthotopic liver transplantation

2004

Ischemic-type biliary lesions are a major complication following orthotopic liver transplantation. They occur in up to 26% of liver transplant recipients. Among other factors, unknown immunologic factors have always been assumed to be partly responsible for these lesions. CC-chemokines and their receptors play a key role in postoperative immunomodulation after liver transplantation. The non-function CC-chemokine receptor 5Δ32 polymorphism (CCR5Δ32) has been shown to lead to a lower rate of acute rejection after kidney transplantation; in liver transplantation the role of CCR5Δ32 is unclear. We investigated the influence of the CCR5Δ32 after liver transplantation with special regard to ische…

Erythropoietin and its lost receptor [8]

2007

Damping excessive inflammation and tissue damage in Mycobacterium tuberculosis infection by Toll IL-1 receptor 8/single Ig IL-1-related receptor, a n…

2007

Abstract Toll IL-1R 8/single Ig IL-1-related receptor (TIR8/SIGIRR) is a member of the IL-1R family, expressed by epithelial tissues and immature dendritic cells, and is regarded as a negative regulator of TLR/IL-1R signaling. Tir8-deficient mice were rapidly killed by intranasal administration of low doses of Mycobacterium tuberculosis, despite controlling efficiently the number of viable bacilli in different organs. Tir8−/−-infected mice showed an increased number of neutrophils and macrophages in the lungs; however, mycobacteria-specific CD4 and CD8 T cells were similar in Tir8−/− and Tir8+/+ mice. Exaggerated mortality of Tir8−/− mice was due to massive liver necrosis and was accompanie…

Biology of gama delta T Cells in Tuberculosis and Malaria

2002

Tuberculosis and malaria remain the leading causes of mortality among human infectious diseases in the world. It is estimated that 3 to 5 million people die from tuberculosis and malaria each year. Although it is traditionally believed that CD4 and CD8 alphabeta T lymphocytes are mandatory for protective immune responses against Mycobacterium tuberculosis and Plasmodium falciparum (the ethiologic agents of tuberculosis and the most severe form of malaria, respectively), there is still incomplete understanding of the mechanisms of immune protection and of the causes of its failure in the affected patients. Several studies in humans and animal models have suggested that Vgamma9/Vdelta2 T cell…

Mycobacterium tuberculosis secretory proteins downregulate T cell activation by interfering with proximal and downstream T cell signalling events

2015

Background Mycobacterium tuberculosis (M. tuberculosis) modulates host immune response, mainly T cell responses for its own survival leading to disease or latent infection. The molecules and mechanisms utilized to accomplish immune subversion by M. tuberculosis are not fully understood. Understanding the molecular mechanism of T cell response to M. tuberculosis is important for development of efficacious vaccine against TB. Methods Here, we investigated effect of M. tuberculosis antigens Ag85A and ESAT-6 on T cell signalling events in CD3/CD28 induced Peripheral blood mononuclear cells (PBMCs) of PPD+ve healthy individuals and pulmonary TB patients. We studied CD3 induced intracellular calc…

Ratios between VEGF ligands and receptors in tumor and stroma have impact on the outcome in resectable NSCLC.

2013

e22147 Background: In tumor angiogenesis there is a complex interplay between endothelial, stromal and tumor cells. Some key regulators of this process are the members of the vascular endothelial growth factor (VEGF) family of ligands and receptors and the neuropilins (NRP). This study analyzes the correlations between the expression of these angiogenic factors in tumor cells and tumor stroma, and their prognostic role in tissue samples from resected non-small cell lung cancer (NSCLC) patients. Methods: Representative tumor and stroma areas from FFPE tissue samples of 125 early-stage NSCLC patients were carefully micro-dissected. RNA isolated from the samples was retrotranscripted and prea…