Search results for "tlr4"
showing 10 items of 96 documents
LPS-mediated production of pro/anti-inflammatory cytokines and eicosanoids in whole blood samples: Biological effects of +896A/G TLR4 polymorphism in…
2011
Toll-like receptors (TLRs) are the principal mediators of rapid microbial recognition: the lipopolysaccharide (LPS) receptor TLR4 seems to have a paradigmatic role. Single nucleotide polymorphisms (SNPs) in the TLR4 gene, such as +896A/G, known to attenuate receptor signaling, have been described. The +896A/G SNP is significantly less frequent in patients with myocardial infarction, Alzheimer's disease or prostate cancer, whereas it is overrepresented in centenarians. To clarify and confirm the biological effects of +896A/G SNP and its role in the pathophysiology of age-related diseases and longevity, we assessed the levels of IL-6, TNF-α, IL-10 and eicosanoids (LTB4 and PGE2) in LPS-stimul…
Role of TLR4 polymorphisms in inflammatory responses: implications for unsuccessful aging.
2007
The total burden of infection at various sites may affect the progression of atherosclerosis and Alzheimer's disease (AD), the risk being modulated by host genotype. The role of lipopolysaccharide (LPS) receptor TLR4 is paradigmatic. It initiates the innate immune response against gram-negative bacteria, and TLR4 single nucleotide polymorphisms (SNPs), such as +896A/G, known to attenuate receptor signaling, have been described. This SNP shows a significantly lower frequency in patients affected by myocardial infarction or AD. Thus, people genetically predisposed to developing lower inflammatory activity seem to have less chance of developing cardiovascular disease (CVD) or AD. In the presen…
Inflammation, Longevity, and Cardiovascular Diseases: Role of Polymorphisms of TLR4
2006
The total burden of infection at various sites may affect the progression of atherosclerosis, the risk being modulated by host genotype. The role of lipopolysaccaride receptor TLR4 is paradigmatic. It initiates the innate immune response against gram-negative bacteria; and TLR4 polymorphisms, as ASP299GLY, suggested to attenuate receptor signaling, have been described. We demonstrated that TLR4 ASP299GLY polymorphism shows a significantly lower frequency in patients affected by myocardial infarction compared to controls, whereas centenarians show a higher frequency. Thus, people genetically predisposed to developing weak inflammatory activity, seem to have fewer chances of developing cardio…
Distinct single-component adjuvants steer human DC-mediated T-cell polarization via Toll-like receptor signaling toward a potent antiviral immune res…
2021
Significance Vaccines profit from the addition of adjuvants to better and more specifically initiate, amplify, and shape immune responses. Although the number of adjuvant candidates has steadily increased, peaking in the current SARS-CoV-2 pandemic, little is known about their inherent mode of action. Using human blood immune cells, we established a multilayer method to systematically assess the adjuvants’ effects on innate and adaptive immune cells. By employing a multiplex analysis with cells from 30 different donors, we determined important patterns of adjuvant function. Moreover, we demonstrate correlates of an antiviral immune response using a Toll-like receptor 7/8 ligand adjuvant and…
Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics
2015
Abstract Background Reduced innate immunity responses as well as reduced T regulatory activities characterise bronchial asthma. Objectives In this study the effect of budesonide on the expression of TLR4 and TLR2 in T regulatory lymphocyte sub-population was assessed. Methods TLR4 and TLR2 expression in total peripheral blood mononuclear cells (PBMC), in CD4+/CD25+ and in CD4+/CD25− was evaluated, by flow cytometric analysis, in mild intermittent asthmatics (n = 14) and in controls (n = 11). The in vitro effects of budesonide in modulating: TLR4 and TLR2 expression in controls and in asthmatics; IL-10 expression and cytokine release (IL-6 and TNF-α selected by a multiplex assay) in asthmati…
Role of TLR4 Receptor Polymorphisms in Boutonneuse Fever
2005
The genetics of the interaction between host and microbes plays an essential role in the survival of the individual and attainment of longevity. The activation of toll-like receptor (TLR)4 plays a key role in natural and clonotypic immune responses. We evaluated whether TLR4 genotype is a component of genetic background protective versus rickettsiosis and whether this background influences longevity. We genotyped for +896A/G TLR4 polymorphism 78 patients affected by Boutonneuse fever, 78 age-matched controls and 78 advanced age individuals from Sicily. The +869G allele, that attenuates receptor signalling, was significantly overrepresented in patients in comparison with age-matched control…
Evidences of +896 A/G TLR4 Polymorphism as an Indicative of Prevalence of Complications in T2DM Patients
2014
T2DM is today considered as world-wide health problem, with complications responsible of an enhanced mortality and morbidity. Thus, new strategies for its prevention and therapy are necessary. For this reason, the research interest has focused its attention on TLR4 and its polymorphisms, particularly the rs4986790. However, no conclusive findings have been reported until now about the role of this polymorphism in development of T2DM and its complications, even if a recent meta-analysis showed its T2DM association in Caucasians. In this study, we sought to evaluate the weight of rs4986790 polymorphism in the risk of the major T2DM complications, including 367 T2DM patients complicated for th…
Study of the antitumor effect of inducible nitric oxide synthase in a breast cancer model : analysis of molecular mechanisms
2013
The anti -tumor effect of a lipid A, OM -174 (lipid portion of LPS) was studied in a model of breast cancer in mice. In vivo, OM- 174 increases the survival of mice whereas in vitro it is not toxic to cancer cells. OM -174 binds to TLR4 immune cells inducing the production of cytokines such as IFNγ. In vitro, the combination of IFNγ to lipid A is cytotoxic. The objective of this thesis is to analyze those molecular mechanisms. We have shown both in vitro and in vivo that the cytotoxicity of the lipid A / IFNγ is dependent of TLR4 and of the receptor for IFNγ, and the NOS II expression. We also showed that the radical species, NO and superoxide anion forming peroxynitrite play a crucial role…
Alzheimer’s disease and genetics of inflammation: a pharmacogenomic vision
2007
Inflammation plays a key role in Alzheimer disease, and dissecting the genetics of inflammation may provide an answer to the possible treatment. The next-generation therapy is based on a pharmacogenomics that will reconure new approaches to a drug used on definite people with specific dosage. The translation of pharmacogenomics into clinical practice will allow bold steps to be taken toward personalized medicine. In response to tissue injury elicited by trauma or infection, the inflammatory response sets in as a complex network of molecular and cellular interactions, directed to facilitate a return to physiological homeostasis and tissue repair. The role of an individual’s genetic backgroun…
Cigarette smoke alters IL-33 expression and release in airway epithelial cells
2014
AbstractAirway epithelium is a regulator of innate immune responses to a variety of insults including cigarette smoke. Cigarette smoke alters the expression and the activation of Toll Like Receptor 4 (TLR4), an innate immunity receptor. IL-33, an alarmin, increases innate immunity Th2 responses. The aims of this study were to explore whether mini-bronchoalveolar lavage (mini-BAL) or sera from smokers have altered concentrations of IL-33 and whether cigarette smoke extracts (CSE) alter both intracellular expression (mRNA and protein) and release of IL-33 in bronchial epithelial cells. The role of TLR4 in the expression of IL-33 was also explored.Mini-BALs, but not sera, from smokers show red…