Blockade of Ca3 calcium channels and induction of G/G cell cycle arrest in colon cancer cells by gossypol.

Background And Purpose: Gastrointestinal tumours overexpress voltage-gated calcium (Ca3) channels (Ca3.1, 3.2 and 3.

Human peripheral blood mononuclear cells display a temporal evolving inflammatory profile after myocardial infarction and modify myocardial fibroblasts phenotype.

Pathophysiological response after acute myocardial infarction (AMI) is described as a three-stage model involving temporal phenotypic modifications of both immune cells and fibroblasts: a primary inflammatory phase, followed by a reparative phase and a fibrous scar maturation phase. Purinergic receptors, particularly the P2Y11 receptor, have been reported to be involved in the regulation of inflammation after ischemia and could act for the resolution of inflammation after AMI. For the first time, we characterized the immuno-inflammatory and P2Y11 expression profiles of peripheral blood mononuclear cells (PBMC) from AMI patients and analyzed the consequences of presenting these cells to cardiac fibroblasts in vitro.

Constitutive and induced forms of membrane-bound proteinase 3 interact with antineutrophil cytoplasmic antibodies and promote immune activation of neutrophils.

Proteinase 3 (PR3) is the main target antigen of antineutrophil cytoplasmic antibodies (ANCAs) in PR3-ANCA-associated vasculitis. A small fraction of PR3 is constitutively exposed on the surface of quiescent blood neutrophils in a proteolytically inactive form. When activated, neutrophils expose an induced form of membrane-bound PR3 (PR3) on their surface as well, which is enzymatically less active than unbound PR3 in solution due to its altered conformation.

Voltage-Gated Sodium Channel Na1.5 Controls NHE-1-Dependent Invasive Properties in Colon Cancer Cells.

Colorectal cancer (CRC) is the second leading cause of death worldwide, with 0.9 million deaths per year. The metastatic stage of the disease is identified in about 20% of cases at the first diagnosis and is associated with low patient-survival rates.

High extracellular sodium chloride concentrations induce resistance to LPS signal in human dendritic cells.

Recent evidence showed that in response to elevated sodium dietary intakes, many body tissues retain Na ions for long periods of time and can reach concentrations up to 200 mM. This could modulate the immune system and be responsible for several diseases. However, studies brought contrasted results and the effects of external sodium on human dendritic cell (DC) responses to danger signals remain largely unknown.

The envelope protein of Zika virus interacts with apolipoprotein E early in the infectious cycle and this interaction is conserved on the secreted viral particles.

Background: Zika virus (ZIKV), a member of the Flaviviridae family, has caused massive outbreaks of infection in tropical areas over the last decade and has now begun spreading to temperate countries. Little is currently known about the specific host factors involved in the intracellular life cycle of ZIKV. Flaviviridae viruses interact closely with host-cell lipid metabolism and associated secretory pathways.

P2x4 receptor promotes mammary cancer progression by sustaining autophagy and associated mesenchymal transition.

Metastatic progression is a major burden for breast cancer patients and is associated with the ability of cancer cells to overcome stressful conditions, such as nutrients deprivation and hypoxia, and to gain invasive properties. Autophagy and epithelial-to-mesenchymal transition are critical contributors to these processes. Here, we show that the P2X4 purinergic receptor is upregulated in breast cancer biopsies from patients and it is primarily localised in endolysosomes.

Quantitative analysis of the formation of nucleoprotein complexes between HIV-1 Gag protein and genomic RNA using transmission electron microscopy.

In HIV, the polyprotein precursor Gag orchestrates the formation of the viral capsid. In the current view of this viral assembly, Gag forms low-order oligomers that bind to the viral genomic RNA triggering the formation of high-ordered ribonucleoprotein complexes. However, this assembly model was established using biochemical or imaging methods that do not describe the cellular location hosting Gag-gRNA complex nor distinguish gRNA packaging in single particles.

The Voltage-Gated Sodium Channel Beta4 Subunit Maintains Epithelial Phenotype in Mammary Cells.

The gene, coding for the Naβ4 subunit of voltage-gated sodium channels, was recently found to be expressed in normal epithelial cells and down-regulated in several cancers. However, its function in normal epithelial cells has not been characterized. In this study, we demonstrated that reducing Naβ4 expression in MCF10A non-cancer mammary epithelial cells generated important morphological changes observed both in two-dimensional cultures and in three-dimensional cysts.

4C3 Human Monoclonal Antibody: A Proof of Concept for Non-pathogenic Proteinase 3 Anti-neutrophil Cytoplasmic Antibodies in Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a severe autoimmune vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA) mainly targeting proteinase 3 (PR3), a neutrophilic serine proteinase. PR3-ANCA binding to membrane-bound PR3 on neutrophils induce their auto-immune activation responsible for vascular lesions. However, the correlation between PR3-ANCA level and disease activity remains inconsistent, suggesting the existence of non-pathogenic PR3-ANCA.

Rock inhibition promotes Na1.5 sodium channel-dependent SW620 colon cancer cell invasiveness.

The acquisition of invasive capacities by carcinoma cells, i.e. their ability to migrate through and to remodel extracellular matrices, is a determinant process leading to their dissemination and to the development of metastases.

Hepatitis B Virus Core Protein Domains Essential for Viral Capsid Assembly in a Cellular Context.

Hepatitis B virus (HBV) core protein (HBc) is essential to the formation of the HBV capsid. HBc contains two domains: the N-terminal domain corresponding to residues 1-140 essential to form the icosahedral shell and the C-terminal domain corresponding to a basic and phosphorylated peptide, and required for DNA replication. The role of these two domains for HBV capsid assembly was essentially studied in vitro with HBc purified from mammalian or non-mammalian cell lysates, but their respective role in living cells remains to be clarified.

BAY 41-4109-mediated aggregation of assembled and misassembled HBV capsids in cells revealed by electron microscopy.

HBc is a small protein essential for the formation of the icosahedral HBV capsid. Its multiple roles in the replication cycle make this protein a promising target for the development of antiviral molecules. Based on the structure of HBc, a series of HBV assembly inhibitors, also known as capsid assembly modulators, were identified.

CMV-infected kidney grafts drive the expansion of blood-borne CMV-specific T cells restricted by shared class I HLA molecules via presentation on donor cells.

We aimed to determine the role of cytomegalovirus (CMV)-infected donor cells in the development of a CMV-specific immune response in kidney transplant recipients. We assessed the CMV pp65-specific immune response by using interferon-ɣ ELISPOT and dextramers in peripheral blood mononuclear cells from 115 recipients (D+R- 31, D+R + 44, D-R + 40) late after transplantation (mean 59 ± 42 months). Receiving a kidney from a D+ donor resulted in a higher number of IFN-ɣ-producing anti-CMV T cells (P = .

Immune deficiency-related enteropathy-lymphocytopenia-alopecia syndrome results from tetratricopeptide repeat domain 7A deficiency.

Background: Inflammatory bowel disease (IBD) is one of the most common chronic gastrointestinal diseases, but the underlying molecular mechanisms remain largely unknown. Studies of monogenic diseases can provide insight into the pathogenesis of IBD.

Objective: We thought to determine the underlying molecular causes of IBD occurring in 2 unrelated families in association with an immune deficiency.

IL-2 phosphorylates STAT5 to drive IFN-γ production and activation of human dendritic cells.

Human dendritic cells (hDCs) produce IL-2 and express IL-2R α-chain (CD25), but the role of IL-2 in DC functions is not well defined. A recent study suggested that the main function of CD25 on hDCs was to transpresent IL-2 to activate T lymphocytes. Our results demonstrate the expression of the three chains of the IL-2R on hDCs and that IL-2 induces STAT5 phosphorylation.

TTC7A mutations disrupt intestinal epithelial apicobasal polarity.

Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is sometimes associated with a combined immunodeficiency (CID), leading to increased susceptibility to infections. The factors underlying this rare disease are poorly understood. We characterized the immunological and intestinal features of 6 unrelated MIA-CID patients.

Mycophenolic acid-treated dendritic cells generate regulatory CD4+ T cells that suppress CD8+ T cells' allocytotoxicity.

Regulatory T cells (Treg) play a crucial role in controlling immunity and transplant rejection. Two main groups of Treg have been described: antigen-induced Treg (iTreg) and natural Treg (nTreg). The ways to induce and the mechanisms of action of Treg subsets remained ill defined, particularly for their effects on CD8(+) T cells.

Pharmacokinetic and pharmacodynamic studies of two different rabbit antithymocyte globulin dosing regimens: results of a randomized trial.

Rabbit antithymocyte globulin (rATG; Thymoglobulin(®)) is currently used to prevent acute rejection in kidney transplantation. The dose and regimen of rATG have not been optimized. Moreover, the impact of different treatment regimens on T-cell phenotype reconstitution remains unknown.

Polymerase ε1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature ("FILS syndrome").

DNA polymerase ε (Polε) is a large, four-subunit polymerase that is conserved throughout the eukaryotes. Its primary function is to synthesize DNA at the leading strand during replication. It is also involved in a wide variety of fundamental cellular processes, including cell cycle progression and DNA repair/recombination.

Interferon gamma licensing of human dendritic cells in T-helper-independent CD8+ alloimmunity.

The high frequency of allogeneic reactive CD8(+) T cells in human and their resistance to immunosuppression might be one of the reasons why successful tolerance-inducing strategies in rodents have failed in primates. Studies on the requirement for T-helper cells in priming CD8(+) T-cell responses have led to disparate findings. Recent studies have reported CD8(+)-mediated allograft rejection independently of T-helper cells; however, the mechanisms that govern the activation of these T cells are far from being elucidated.

Mycophenolic acid differentially affects dendritic cell maturation induced by tumor necrosis factor-alpha and lipopolysaccharide through a different modulation of MAPK signaling.

Mycophenolic acid (MPA) is an immunosuppressive drug which induces resistance to several maturation signals in human dendritic cells (DC) by unknown mechanisms. As mitogen-activated protein kinases (MAPK) are involved in the maturation process, we studied whether MPA affected p38MAPK and extracellular signal-regulated kinase (ERK1/2) in human DC. We first showed that MPA reduced TNFalpha-induced phenotype maturation, whereas it had no effect after LPS activation, suggesting that MPA preferentially affects the signaling pathway used by TNFalpha.