Search results for "P38"

Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and …

2019

Immunomodulatory glycolipids, among which α-galactosylceramide (KRN7000) is an iconic example, have shown strong therapeutic potential in a variety of conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases. A main difficulty for those channels is that they often provoke a cytokine storm comprising both pro- and anti-inflammatory mediators that antagonize each other and negatively affect the immune response. The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hamper…

Mycobacterial antigen(s) induce anergy by altering TCR- and TCR/CD28-induced signalling events: insights into T-cell unresponsiveness in leprosy.

2009

Present study investigates the role of Mycobacterium leprae (M. leprae) antigens on TCR- and TCR/CD28-induced signalling leading to T-cell activation and further correlates these early biochemical events with T-cell anergy, as prevailed in advanced stages of leprosy. We observed that both whole cell lystae (WCL) and soluble fraction of M. leprae sonicate (MLSA) not only inhibited TCR, thapsigargin and ionomycin induced calcium fluxes by diminishing the opening of calcium channels, but also TCR- or TCR/CD28-induced proximal signalling events like phosphorylation of Zap-70 and protein kinase-C (PKC) activity. Study of TCR- and TCR/CD28-induced downstream signals revealed that M. leprae antige…

Gamma interferon administration differently affects sensitive or doxorubicin resistant P388 leukemia cells; a relationship with antioxidant defenses?

1989

To the research of treatments for the typical calcific disease of old aortic valve in the omics era: Is the miR-195 a therapeutic signature via targe…

2020

Calcific aortic valve disease (CAVD) is the most frequent form of val-vular pathology [1,2], with high percentages of mortality and morbidityin Western populations, so much to be a very public health problem [2].Diverse millions of subjects are affected by CAVD and the major numberare old individuals (65- older), even if some have a younger age and aregenerally affected by congenital bicuspid aortic valve (BAV) disease[2,3]. CAVD in BAV individuals arises decades earlier respect to subjectswith the physiological tricuspid aortic valve [3]. Furthermore, it can leadto death if untreated with surgical aortic valve replacement or trans-catheter aortic valve implantation, its unique treatments […

Neuronal cell cycle: the neuron itself and its circumstances.

2015

Neurons are usually regarded as postmitotic cells that undergo apoptosis in response to cell cycle reactivation. Nevertheless, recent evidence indicates the existence of a defined developmental program that induces DNA replication in specific populations of neurons, which remain in a tetraploid state for the rest of their adult life. Similarly, de novo neuronal tetraploidization has also been described in the adult brain as an early hallmark of neurodegeneration. The aim of this review is to integrate these recent developments in the context of cell cycle regulation and apoptotic cell death in neurons. We conclude that a variety of mechanisms exists in neuronal cells for G1/S and G2/M check…

Dynamic Antigen Presentation Patterns of Listeria monocytogenes-Derived CD8 T Cell Epitopes In Vivo

2001

Abstract Little information exists regarding the presentation of antigenic peptides in infected tissues. In this study the in vivo presentation of four different CD8 T cell epitopes of Listeria monocytogenes was monitored. Peptide presentation was measured by a new, highly sensitive, ex vivo Ag presentation assay that was based on the testing of freshly isolated cells from infected spleens with peptide-specific CD8 T cell lines in an IFN-γ-specific ELISPOT assay. Remarkably, the peptide presentation pattern of splenocytes and that of macrophages purified from spleens of L. monocytogenes-infected mice were different from those of in vitro infected macrophage-like cell lines. The in vivo Ag p…

N-acetyl-L-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A…

2011

64% of chronic obstructive pulmonary disease (COPD) exacerbations are caused by respiratory infections including influenza (strains A and B) and respiratory syncytial virus (RSV). They affect the airway epithelium increasing inflammatory and apoptosis events through mechanisms involving ROS generation, and induce the release of mucins from epithelial cells that are involved in the deterioration of the patient's health during the course of the disease. The antioxidant NAC has proved useful in the management of COPD reducing symptoms, exacerbations and accelerated lung function decline. It has been shown to inhibit influenza virus replication and to diminish the release of inflammatory and ap…

Specific and global regulation of mRNA stability during osmotic stress in Saccharomyces cerevisiae.

2009

Hyperosmotic stress yields reprogramming of gene expression in Saccharomyces cerevisiae cells. Most of this response is orchestrated by Hog1, a stress-activated, mitogen-activated protein kinase (MAPK) homologous to human p38. We investigated, on a genomic scale, the contribution of changes in transcription rates and mRNA stabilities to the modulation of mRNA amounts during the response to osmotic stress in wild-type and hog1 mutant cells. Mild osmotic shock induces a broad mRNA destabilization; however, osmo-mRNAs are up-regulated by increasing both transcription rates and mRNA half-lives. In contrast, mild or severe osmotic stress in hog1 mutants, or severe osmotic stress in wild-type cel…

Dual role of the p38 MAPK/cPLA2 pathway in the regulation of platelet apoptosis induced by ABT-737 and strong platelet agonists.

2013

p38 Mitogen-activated protein (MAP) kinase is involved in the apoptosis of nucleated cells. Although platelets are anucleated cells, apoptotic proteins have been shown to regulate platelet lifespan. However, the involvement of p38 MAP kinase in platelet apoptosis is not yet clearly defined. Therefore, we investigated the role of p38 MAP kinase in apoptosis induced by a mimetic of BH3-only proteins, ABT-737, and in apoptosis-like events induced by such strong platelet agonists as thrombin in combination with convulxin (Thr/Cvx), both of which result in p38 MAP kinase phosphorylation and activation. A p38 inhibitor (SB202190) inhibited the apoptotic events induced by ABT-737 but did not influ…

Activation of cGMP-dependent Protein Kinase Iβ Inhibits Interleukin 2 Release and Proliferation of T Cell Receptor-stimulated Human Peripheral T Cells

2000

Several major functions of type I cGMP-dependent protein kinase (cGK I) have been established in smooth muscle cells, platelets, endothelial cells, and cardiac myocytes. Here we demonstrate that cGK Ibeta is endogenously expressed in freshly purified human peripheral blood T lymphocytes and inhibits their proliferation and interleukin 2 release. Incubation of human T cells with the NO donor, sodium nitroprusside, or the membrane-permeant cGMP analogs PET-cGMP and 8-pCPT-cGMP, activated cGK I and produced (i) a distinct pattern of phosphorylation of vasodilator-stimulated phosphoprotein, (ii) stimulation of the mitogen-activated protein kinases ERK1/2 and p38 kinase, and, upon anti-CD3 stimu…