Search results for "toll"

Aging Successfully: The Role of Genetics and Environment in the Era of the Aging-Boom. Potential Therapeutic Implications

2019

Aging is one of the main health-related challenges in the world. The average life expectancy of the global population at birth is increasing up to 72 years, in 2016 and it increases about two years every decade. The healthcare costs in many countries are very high because of the increased number of unhealthy populations, and the consequent increase of severe age-related disabilities [1]. Therefore, the goal of the future should be the achievement of the so-called “health-span” (healthy-life-span), more than the treatment of age-related disease to prevent the collapse of the health system. In order to achieve this objective, it is necessary to identify new targets and biomarkers and to addre…

Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4

2012

Ingestion of wheat, barley, or rye triggers small intestinal inflammation in patients with celiac disease. Specifically, the storage proteins of these cereals (gluten) elicit an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 as major genetic predisposition. This well-defined role of adaptive immunity contrasts with an ill-defined component of innate immunity in celiac disease. We identify the α-amylase/trypsin inhibitors (ATIs) CM3 and 0.19, pest resistance molecules in wheat, as strong activators of innate immune responses in monocytes, macrophages, and dendritic cells. ATIs engage the TLR4–MD2–CD14 complex and lead to up-regulation of maturation markers a…

Role of the Netrin-like Domain of Procollagen C-Proteinase Enhancer-1 in the Control of Metalloproteinase Activity

2010

The netrin-like (NTR) domain is a feature of several extracellular proteins, most notably the N-terminal domain of tissue inhibitors of metalloproteinases (TIMPs), where it functions as a strong inhibitor of matrix metalloproteinases and some other members of the metzincin superfamily. The presence of a C-terminal NTR domain in procollagen C-proteinase enhancers (PCPEs), proteins that stimulate the activity of astacin-like tolloid proteinases, raises the possibility that this might also have inhibitory activity. Here we show that both long and short forms of the PCPE-1 NTR domain, the latter beginning at the N-terminal cysteine known to be critical for TIMP activity, show no inhibition, at …

The gut microbiota - a modulator of endothelial cell function and a contributing environmental factor to arterial thrombosis.

2019

Introduction: There is emerging evidence linking the commensal gut microbiota with the development of cardiovascular disease and arterial thrombosis. In immunothrombosis, the host clotting system protects against the dissemination of invading microbes, not considering the huge number of microbes that interact with host physiology in a mutualistic fashion. Areas covered: Interestingly, recent research revealed that colonizing gut microbes profoundly influence host innate immune pathways that support arterial thrombus growth. The gut microbiota promotes arterial thrombus formation by enhancing the pro-adhesive capacity of the vascular endothelium, triggering hepatic von Willebrand factor synt…

The many roads to inflammatory bowel diseases.

2006

Two independent studies by Rakoff-Nahoum et al. (2006) and Uhlig et al. (2006) in this issue of Immunity have illuminated a unique pathogenic role of innate immunity via Toll-like receptor and interleukin-23 signaling, respectively, in intestinal inflammation. These data define new roads to gut inflammation and future avenues for therapy.

Molecular approaches in autoimmunity and ageing: potential implications for future therapies.

My researches during my PhD were mainly focused on two aspects. The first one, was to study molecular aspects potentially implicated in autoimmunity pathogenesis, in order to identify new potential risk factors useful as therapeutic target. To this end, we focused on two severe and wasting systemic autoimmune diseases: systemic lupus erythematosus and systemic sclerosis. Pathogenesis of these diseases has still not clear and early diagnosis is difficult to identify because of complex and heterogeneous presentation of symptoms. A strong genetic association between HLA and disease susceptibility is well accept, nevertheless, other factors as oxidative stress, KIR and inflammatory cytokines ha…

Consensus guidelines for the detection of immunogenic cell death

2014

Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defect…

European leaders unmasked: Covid-19 communication strategy through Twitter

2020

[EN] The coronavirus disease Covid-19 (SARS-CoV-2) pandemic is exacting a huge toll on individuals, families, communities, and societies across the world. The study of public communication is a key aspect for slowing the spread of the virus and therefore reducing the death rate. This article analyses political leaders' crisis communication during the Covid-19 pandemic of the most affected European countries, Boris Johnson (United Kingdom), Emmanuel Macron (France), Pedro Sanchez (Spain) and Giuseppe Conte (Italy), in addition to Tedros Adhanom as a representative of the World Health Organisation (WHO) and Ursula Von der Leyen President of the European Union (EU). The study focuses on the vi…

Direct Toll-Like Receptor-Mediated Stimulation of Hematopoietic Stem and Progenitor Cells Occurs In Vivo and Promotes Differentiation Toward Macropha…

2012

Abstract As Toll-like receptors (TLRs) are expressed by hematopoietic stem and progenitor cells (HSPCs), they may play a role in hematopoiesis in response to pathogens during infection. We show here that TLR2, TLR4, and TLR9 agonists (tripalmitoyl-S-glyceryl-L-Cys-Ser-(Lys)4 [Pam3CSK4], lipopolysaccharide [LPS], and CpG oligodeoxynucleotide [ODN]) induce the in vitro differentiation of purified murine lineage negative cells (Lin−) as well as HSPCs (identified as Lin− c-Kit+ Sca-1+ IL-7Rα− [LKS] cells) toward macrophages (Mph), through a myeloid differentiation factor 88 (MyD88)-dependent pathway. In order to investigate the possible direct interaction of soluble microorganism-associated mol…

Hypoallergenic fragment of Par j 2 increases functional expression of Toll-like receptors in atopic children.

2006

Background: Parietaria judaica (Par j) is one of the main causes of allergy in the Mediterranean countries. The activation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) inhibits nasal inflammation of atopic children. Objective:  To examine, in vivo and in vitro, the effect of recombinant Par j 2 (rPar j 2) and of its fragments (1–55 and 52–102) on atopic children. Methods:  We used skin prick test for in vivo evaluations. We assessed, in vitro, in peripheral blood mononuclear cells (PBMC), the effect of rPar j 2 and of the two fragments on neutrophil chemotaxis, on CD45RO, on TLR2 and TLR4 expression, on LPS binding and on interferon (IFN)-γ release, by a microchemotaxis chambe…