Search results for "ACTIVATION"

The yopJ locus is required for Yersinia-mediated inhibition of NF-kappaB activation and cytokine expression: YopJ contains a eukaryotic SH2-like doma…

1998

Upon exposure to bacteria, eukaryotic cells activate signalling pathways that result in the increased expression of several defence-related genes. Here, we report that the yopJ locus of the enteropathogen Yersinia pseudotuberculosis encodes a protein that inhibits the activation of NF-kappaB transcription factors by a mechanism(s), which prevents the phosphorylation and subsequent degradation of the inhibitor protein IkappaB. Consequently, eukaryotic cells infected with YopJ-expressing Yersinia become impaired in NF-kappaB-dependent cytokine expression. In addition, the blockage of inducible cytokine production coincides with yopJ-dependent induction of apoptosis. Interestingly, the YopJ pr…

Ionizing radiation-induced E-selectin gene expression and tumor cell adhesion is inhibited by lovastatin and all-trans retinoic acid

2004

E-selectin mediated tumor cell adhesion plays an important role in metastasis. Here we show that ionizing radiation (IR) induces E-selectin gene and protein expression in human endothelial cells at therapeutically relevant dose level. E-selectin expression is accompanied by an increase in the adhesion of human colon carcinoma cells to primary human umbilical vein endothelial cells (HUVEC). The HMG-CoA reductase inhibitor lovastatin impairs IR-stimulated E-selectin expression as analyzed at the level of the protein, mRNA and promoter. Inactivation of Rho GTPases either by use of Clostridium difficile toxin A or by co-expression of dominant-negative Rho blocked IR-induced E-selectin gene indu…

Release of dendritic cells from cognate CD4 + T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimm…

2012

Resting dendritic cells (DCs) induce tolerance of peripheral T cells that have escaped thymic negative selection and thus contribute significantly to protection against autoimmunity. We recently showed that CD4 + Foxp3 + regulatory T cells (Tregs) are important for maintaining the steady-state phenotype of DCs and their tolerizing capacity in vivo. We now provide evidence that DC activation in the absence of Tregs is a direct consequence of missing DC–Treg interactions rather than being secondary to generalized autoimmunity in Treg-less mice. We show that DCs that lack MHC class II and thus cannot make cognate interactions with CD4 + T cells are completely unable to induce peripheral CD8 +…

Noisy dynamics in long and short Josephson junctions

The study of nonlinear dynamics in long Josephson junctions and the features of a particular kind of junction realized using a graphene layer, are the main topics of this research work. The superconducting state of a Josephson junction is a metastable state, and the switching to the resistive state is directly related to characteristic macroscopic quantities, such as the current the voltage across the junction, and the magnetic field through it. Noise sources can affect the mean lifetime of this superconducting metastable state, so that noise induced effects on the transient dynamics of these systems should be taken into account. The long Josephson junctions are investigated in the sine-Gor…

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 …

Solvent-trap reaction of triazolinediones with simple alkenes: An experimental/theoretical study of thermodynamic and kinetic parameters This work is…

2015

The reaction of N-phenyltriazolinedione with simple alkyl-substituted alkenes in a series of simple alcohols as nucleophilic solvents affords two products: a solvent-addition product (trap) and the ene adduct. Herein we present different experimental data which allow the estimation of different kinetic parameters (ΔΔH ≠ene,trap and ΔΔS ≠ene,trap ). The values of those parameters are found to be lower with a longer nucleophile-solvent molecule. Solvent isotope effects are also estimated and found in favour of the heavier (and smaller) deuterated compounds. Results from competition experiments in equimolar binary mixtures of different alcohols as solvents also point to the prevalence of the s…

Switch between tyrosinase and catecholoxidase activity of scorpion hemocyanin by allosteric effectors

2008

AbstractPhenoloxidases and hemocyanins have similar type 3 copper centers although they perform different functions. Hemocyanins are oxygen carriers, while phenoloxidases (tyrosinase/catecholoxidase) catalyze the initial step in melanin synthesis. Tyrosinases catalyze two subsequent reactions, whereas catecholoxidases catalyze only the second one. Recent results indicate that hemocyanins can also function as phenoloxidases and here we show for the first time that hemocyanin can be converted to phenoloxidase. Furthermore, its substrate specificity can be switched between catecholoxidase and tyrosinase activity depending on effectors such as hydroxymethyl-aminomethan (Tris) and Mg2+-ions. Thi…

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…

Plasmacytoid dendritic cells are inefficient in activation of human regulatory T cells

2011

BACKGROUND: Dendritic cells (DC) play a key role in initiation and regulation of immune responses. Plasmacytoid DC (pDC), a small subset of DC, characterized as type-I interferon producing cells, are critically involved in anti-viral immune responses, but also mediate tolerance by induction of regulatory T cells (Treg). In this study, we compared the capacity of human pDC and conventional DC (cDC) to modulate T cell activity in presence of Foxp3(+) Treg. PRINCIPAL FINDINGS: In coculture of T effector cells (Teff) and Treg, activated cDC overcome Treg anergy, abrogate their suppressive function and induce Teff proliferation. In contrast, pDC do not break Treg anergy but induce Teff prolifera…

Acidic Environment Leads to ROS-Induced MAPK Signaling in Cancer Cells

2011

Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e), pH(i)) and mitogen-activated-protein-kinases (ERK1/2, p38) was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i) in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furth…