Search results for "Inflammation."

Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression.

2017

Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial muc…

Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer’s disease

2018

Background: Aβ 1-42 peptide abnormal production is associated with the development and maintenance of neuroinflammation and oxidative stress in brains from Alzheimer disease (AD) patients. Suppression of neuroinflammation may then represent a suitable therapeutic target in AD. We evaluated the efficacy of IFNβ1a in attenuating cognitive impairment and inflammation in an animal model of AD. Methods: A rat model of AD was obtained by intra-hippocampal injection of Aβ 1-42 peptide (23 μg/2 μl). After 6 days, 3.6 μg of IFNβ1a was given subcutaneously (s.c.) for 12 days. Using the novel object recognition (NOR) test, we evaluated changes in cognitive function. Measurement of pro-inflammatory or …

2020

Dendritic cells (DC) play a key role in the adaptive immune response due to their ability to present antigens and stimulate naive T cells. Many bacteria and viruses can efficiently target DC, resulting in impairment of their immunostimulatory function or elimination. Hence, the DC compartment requires replenishment following infection to ensure continued operational readiness of the adaptive immune system. Here, we investigated the molecular and cellular mechanisms of inflammation-induced DC generation. We found that infection with viral and bacterial pathogens as well as Toll-like receptor 9 (TLR9) ligation with CpG-oligodeoxynucleotide (CpG-ODN) expanded an erythropoietin (EPO)-dependent …

Heat shock protein 70 dampens the inflammatory response of human PDL cells to mechanical loading in vitro

2019

BACKGROUND AND OBJECTIVE Previously, we demonstrated an inflammatory response of human PDL (hPDL) cells to mechanical loading. The cellular reaction was dampened by heat pre-treatment suggesting a protective role for heat shock proteins (HSP) during stress-induced ischemia. Here we explored if HSP70, which has already been documented in the pressure zone of tooth movement, might be regulatorily involved in the attenuation of the inflammatory response. MATERIALS AND METHODS Fifth passage hPDL cells were mechanically loaded in the presence of the HSP70 inhibitor VER155008. Cell morphology, HSP70 expression, viability, IL-6 and IL-8 expression were determined by means of microscopy, realtime-P…

Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation

2015

Unwinding DNA and unleasing inflammation Fighting infections often comes with collateral damage, which sometimes can be deadly. For instance, in septic shock, the overwhelming release of inflammatory mediators drives multi-organ failure. Rialdi et al. now report a potential new therapeutic target for controlling excessive inflammation: the DNA unwinding enzyme topoisomerase I (Top1) (see the Perspective by Pope and Medzhitov). Upon infection, Top1 specifically localizes to the promoters of pathogen-induced genes and promotes their transcription by helping to recruit RNA polymerase II. Pharmacological inhibition of Top1 in a therapeutic setting increased survival in several mouse models of s…

Inflammation and the coagulation system in tuberculosis: Tissue Factor leads the dance

2016

Mycobacterium tuberculosis, the causative agent of tuberculosis, drives the formation of granulomas, structures in which both immune cells and the bacterial pathogen cohabit. The most abundant cells in granulomas are macrophages, which contribute as both cells with bactericidal activity and as targets for M. tuberculosis infection and proliferation during the entire course of infection. The mechanisms and factors involved in the regulation and control of macrophage microenvironment-specific polarization and plasticity are not well understood, as some granulomas are able to control bacteria growth and others fail to do so, permitting bacterial spread. In this issue of the European Journal of…

Macrophage Factor Xa Signaling Promotes Cancer Immune Evasion

2018

Abstract Coagulation signaling through protease activated receptors (PARs) participates in inflammation and immunity. In cancer, tissue factor (TF) driven signaling via PAR2 promotes tumor progression, but effective pharmacological strategies to inhibit the PAR2 activating proteases for clinical anti-cancer benefit are currently unknown. To gain a better understanding of signaling by coagulation proteases, we generated PAR2 mouse strains with mutations that abolish canonical proteolysis by all proteases including FVIIa (PAR2 R38E) or create specific resistance to cleavage by the TF-FVIIa-Xa signaling complex (PAR2 G37I) that requires the endothelial cell protein C receptor (EPCR, Procr). As…

MiR-663, a MicroRNA Linked with Inflammation and Cancer That Is under the Influence of Resveratrol

2018

Resveratrol (trans-3,5,4′-trihydroxystilbene, RSV) is a non-flavonoid dietary polyphenol with antioxidant, anti-inflammatory and anti-cancer properties that is primarily found in red berries. While RSV displays many beneficial effects in vitro, its actual effects in vivo or in animal models remain passionately debated. Recent publications suggest that RSV pleiotropic effects could arise from its capability to regulate the expression and activity of microRNAs, short regulators themselves capable of regulating up to several hundreds of target genes. In particular, RSV increases microRNA miR-663 expression in different human cell lines, suggesting that at least some of its multiple benef…

Evolutionary conserved mechanisms pervade structure and transcriptional modulation of allograft inflammatory factor-1 from sea anemone Anemonia virid…

2017

Gene family encoding allograft inflammatory factor-1 (AIF-1) is well conserved among organisms; however, there is limited knowledge in lower organisms. In this study, the first AIF-1 homologue from cnidarians was identified and characterised in the sea anemone Anemonia viridis. The full-length cDNA of AvAIF-1 was of 913 bp with a 5' -untranslated region (UTR) of 148 bp, a 3'-UTR of 315 and an open reading frame (ORF) of 450 bp encoding a polypeptide with149 amino acid residues and predicted molecular weight of about 17 kDa. The predicted protein possesses evolutionary conserved EF hand Ca2+ binding motifs, post-transcriptional modification sites and a 3D structure which can be superimposed …

Thrombo-Inflammation in Cardiovascular Disease

2020

AbstractThrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating …