Search results for "secret"

2019

The massive infiltration of lymphocytes into the skin is a hallmark of numerous human skin disorders. By co-culturing murine keratinocytes with splenic T cells we demonstrate here that T cells affect and control the synthesis and secretion of chemokines by keratinocytes. While pre-activated CD8+T cells induce the synthesis of CXCL9 and CXCL10 in keratinocytes and keep in check the synthesis of CXCL1, CXCL5, and CCL20, keratinocytes dampen the synthesis of CCL3 and CCL4 in pre-activated CD8+T cells. One key molecule is IFN-γ that is synthesized by CD8+T cells under the control of NFATc1 and NFATc2. CD8+T cells deficient for both NFAT factors are unable to induce CXCL9 and CXCL10 expression. …

1-ethyl-3-(6-methylphenanthridine-8-il) urea modulates TLR3/9 activation and induces selective pro-inflammatory cytokine expression in vitro.

2017

We have previously demonstrated the nucleic acid binding capacity of phenanthridine derivatives (PHTs). Because nucleic acids are potent inducers of innate immune response through Toll-like receptors (TLRs), and because PTHs bear a structural resemblance to commonly used synthetic ligands for TLR7/8, we hypothesized that PHTs could modulate/activate immune response. We found that compound M199 induces secretion of IL-6, IL-8 and TNFα in human PBMCs and inhibits TLR3/9 activation in different cellular systems (PBMCs, HEK293 and THP-1 cell lines).

Active and Secretory IgA-Coated Bacterial Fractions Elucidate Dysbiosis in Clostridium difficile Infection

2016

C. difficile is a major enteric pathogen with worldwide distribution. Its expansion is associated with broad-spectrum antibiotics which disturb the normal gut microbiome. In this study, the DNA sequencing of highly active bacteria and bacteria opsonized by intestinal secretory immunoglobulin A (SIgA) separated from the whole bacterial community by FACS elucidated how the gut dysbiosis promotes C. difficile infection (CDI). Bacterial groups with inhibitory effects on C. difficile growth, such as Lactobacillales, were mostly inactive in the CDI patients. C. difficile was typical for the bacterial fraction opsonized by SIgA in patients with CDI, while Fusobacterium was characteristic for the S…

Uptake of polyphosphate microparticles in vitro (SaOS-2 and HUVEC cells) followed by an increase of the intracellular ATP pool size

2017

Recently two approaches were reported that addressed a vitally important problem in regenerative medicine, i. e. the successful treatment of wounds even under diabetic conditions. Accordingly, these studies with diabetic rabbits [Sarojini et al. PLoS One 2017, 12(4):e0174899] and diabetic mice [Müller et al. Polymers 2017, 9, 300] identified a novel (potential) target for the acceleration of wound healing in diabetes. Both studies propose a raise of the intracellular metabolic energy status via exogenous administration either of ATP, encapsulated into lipid vesicles, or of polyphosphate (polyP) micro-/nanoparticles. Recently this physiological polymer, polyP, was found to release metabolic …

Tumor- and cytokine-primed human natural killer cells exhibit distinct phenotypic and transcriptional signatures.

2019

An emerging cellular immunotherapy for cancer is based on the cytolytic activity of natural killer (NK) cells against a wide range of tumors. Although in vitro activation, or "priming," of NK cells by exposure to pro-inflammatory cytokines, such as interleukin (IL)-2, has been extensively studied, the biological consequences of NK cell activation in response to target cell interactions have not been thoroughly characterized. We investigated the consequences of co-incubation with K562, CTV-1, Daudi RPMI-8226, and MCF-7 tumor cell lines on the phenotype, cytokine expression profile, and transcriptome of human NK cells. We observe the downregulation of several activation receptors including CD…

Molecular surveillance of norovirus, 2005–16 : an epidemiological analysis of data collected from the NoroNet network

2018

BACKGROUND: The development of a vaccine for norovirus requires a detailed understanding of global genetic diversity of noroviruses. We analysed their epidemiology and diversity using surveillance data from the NoroNet network.METHODS: We included genetic sequences of norovirus specimens obtained from outbreak investigations and sporadic gastroenteritis cases between 2005 and 2016 in Europe, Asia, Oceania, and Africa. We genotyped norovirus sequences and analysed sequences that overlapped at open reading frame (ORF) 1 and ORF2. Additionally, we assessed the sampling date and country of origin of the first reported sequence to assess when and where novel drift variants originated.FINDINGS: W…

NOTCH signalling in ovarian cancer angiogenesis

2020

The Notch signalling pathway is involved in the new vessel formation process by regulating tip and stalk cells, which are key cells in the sprout formation. This process is essential in both normal ovary and cancer angiogenesis and is regulated by Notch-VEGF crosstalk. Furthermore, Notch has been linked in ovary with stem cell maintenance and epithelial mesenchymal transition processes. Dysregulation of the Notch pathway is frequent in ovarian cancer (OC) and it has been associated with impaired survival and advanced stages or lymph node involvement. Notch also plays a role in chemoresistance to platinum. In this context, this pathway has emerged as an attractive target for precision medici…

Effect of colorectal cancer-derived extracellular vesicles on the immunophenotype and cytokine secretion profile of monocytes and macrophages.

2018

Abstract. Background Macrophages are one of the most important players in the tumor microenvironment. The polarization status of tumor associated macrophages into a pro-inflammatory type M1 or anti-inflammatory type M2 may influence cancer progression and patient survival. Extracellular vesicles (EVs) are membrane-bound vesicles containing different biomolecules that are involved in cell to cell signal transfer. Accumulating evidence suggests that cancer-derived EVs are taken up by macrophages and modulate their phenotype and cytokine profile. However, the interactions of cancer-derived EVs with monocytes and macrophages at various differentiation and polarization states are poorly understo…

Death Receptor 5 Displayed on Extracellular Vesicles Decreases TRAIL Sensitivity of Colon Cancer Cells

2020

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is considered to be a promising antitumor drug because of its selective proapoptotic properties on tumor cells. However, the clinical application of TRAIL is until now limited because of the resistance of several cancer cells, which can occur at various levels in the TRAIL signaling pathway. The role of decoy receptors that can side-track TRAIL, thereby preventing the formation of an activated death receptor, has been extensively studied. In this study, we have focused on extracellular vesicles (EVs) that are known to play a role in cell-to-cell communication and that can be released by donor cells into the medium transferring …

MODULATION OF GRO-ALPHA AND TNF-ALPHA PRODUCTION BY PERIPHERAL BLOOD MONONUCLEAR CELLS TREATED WITH KILLED HELICOBACTER PYLORI.

2007

GRO-alpha seems to play an important role in recruiting and activating neutrophils during Helicobacter pylori infection. In the present study, we examined how treatment with killed H. pylori or/and live H. pylori may differentially influence the in vitro GRO-alpha and TNF-alpha release by peripheral blood mononuclear cells (PBMC). The amounts of TNF-alpha and GRO-alpha produced by PBMC after stimulation with live H. pylori were higher than those produced after stimulation with a combination of killed and live H. pylori and the latter were higher than those produced after stimulation with killed H. pylori. In conclusion, the treatment of peripheral blood mononuclear cells with killed H. pyl…