1,721,033 research outputs found
The dual role of nod-like receptors in mucosal innate immunity and chronic intestinal inflammation
No full textNucleotide-binding and oligomerization domain NOD-like receptors (NLRs) are highly conserved cytosolic pattern recognition receptors that play, in combination with toll-like receptors, a critical role in innate immunity and inflammation. These proteins are characterized by a central oligomerization domain termed nucleotide-binding domain, and a protein interaction domain containing leucine-rich repeats. Some NLRs, including NOD1 and NOD2, sense the cytosolic presence of conserved bacterial molecular signatures and drive the activation of mitogen-activated protein kinase and the transcription factor NF-κB. A different set of NLRs induces caspase-1 activation through the assembly of large protein complexes known as inflammasomes. Activation of NLR proteins results in secretion of pro-inflammatory cytokines and subsequent inflammatory responses. The critical role of NLRs in innate immunity is underscored by the fact that polymorphisms within their genes are implicated in the development of several immune-mediated diseases, including inflammatory bowel disease. Over the past few years, the role of NLRs in intestinal homeostasis has been highlighted, however the mechanism by which dysfunction in these proteins leads to aberrant inflammation is still the focus of much investigation. The purpose of this review is to systematically evaluate the function of NLRs in mucosal innate immunity and understand how genetic or functional alterations in these components can lead to the disruption of intestinal homeostasis, and the subsequent development of chronic inflammation. © 2014 Corridoni, Arseneau, Cifone and Cominelli
Natural-Killer cells in scleroderma
No full textProgressive systemic sclerosis (PSS) is a disease of unknown aetiology. The presence of various immunological abnormalities and clinical overlapping with diseases such as systemic lupus erythematous have led to the characterization of PSS as an autoimmune disease. Involvement of natural killer (NK) cells in the pathophysiology of progressive systemic sclerosis has been considered.
Enhanced NK activity and normal ADCC activity was observed in an homogeneous group of 16 PSS patients with mild progression and a duration of disease > 7 years. Several factors indicate that the observed increase in NK activity could be due to a high number of circulating effector cells. Enumeration of the main effectors of NK activity by morphology and phenotype showed significantly augmented numbers of large granular lymphocytes (LGL) and CD16+ cells. Moreover, the spectrum of target sensitivity to PSS patient cells was unchanged when compared with controls indicating that enhancement may depend on an increase in the number of circulating NK cells rather than their intrinsic activation
Evaluation of the effects of extremely low frequenciy electromagnetic fiels on mammalian follicle development
No full textIL-2-activated rat NK cells express inducible nitric oxide synthase that contributes to cytotoxic function and IFN-g production
No full textNatural killer (NK) cells are large granular lymphocytes capable of destroying cells infected by virus or bacteria and susceptible tumor cells without prior sensitization and restriction by major histocompatability complex (MHC) antigens, Their cytotoxic activity could be strongly enhanced by interleukin-2 (IL-2), Previous findings, even if obtained with indirect experimental approaches, have suggested a possible involvement of the inducible nitric oxide (iNOS) pathway in the NK-mediated target cell killing. The aim of the present study was first to directly examine the induction of iNOS in IL-2-activated rat NK cells isolated from peripheral blood (PB-NK) or spleen (S-NK), and second to investigate the involvement of the iNOS-derived NO in the cytotoxic function of these cells. Our findings clearly indicate the induction of iNOS expression in IL-2-activated PB-NK and S-NK cells, as evaluated either at mRNA and protein levels. Accordingly, significantly high levels of iNOS activity were shown, as detected by the L-arginine to L-citrulline conversion in appropriate assay conditions. The consequent NO generation appears to partially account for NK cell-mediated DNA fragmentation and lysis of sensitive tumor target cells, In fact, functional inhibition of iNOS through specific inhibitors, as well as the almost complete abrogation of its expression through a specific iNOS mRNA oligodeoxynucleotide antisense, significantly reduced the lytic activity of IL-2-activated NK cells. Moreover, IL-2-induced interferon-gamma production appears also to be dependent at least in part, on iNOS induction, (C) 1999 by The American Society of Hematolog
Erk-dependent cytosolic phospholipase activity is induced by cd95 ligand cross-linking in the mouse derived Sertoli cell line TM4 and is required to trigger apoptosis in CD95 bearing cells
No full textIn the present study we demonstrated that CD95L crosslinking generated reverse signalling in the mouse derived Sertoli cell line TM4, Treatment of TM4 cells with mAb anti-CD95L induced activation of the cytosolic phospholipase A(2) (cPLA(2)), Cytosolic PLA, activation was controlled by the MAPK pathway as indicated by the ability of the specific MEK inhibitor, PD098059, to abolish cPLA2 activation, In addition, Western blot experiments showed a rapid increase in phosphorylated Erk1/2 following CD95L cross-linking, while no effect on the phosphorylation of other MAPK, p38 or JNK, was observed, CD95L cross-linking by mAb increased the levels of soluble CD95L and apoptotic activity of TM4 cell supernatants, which was blacked by co-incubation with the PLA, inhibitor, AACOCF3 or PD098059, Finally, pre-treatment of TM4 cells with AACOCF(3) or PD098059 completely abolished TM4-induced apoptosis of Jurkat T cells, thus indicating that the Erk/cPLA(2) pathway is required for CD95L-induced apoptosis
Methods of isolation, characterization and expansion of human adipose-derived stem cells (ASCs): An overview
Get PDFConsidering the increasing interest in adipose-derived stem cells (ASCs) in regenerative medicine, optimization of methods aimed at isolation, characterization, expansion and evaluation of differentiation potential is critical to ensure (a) the quality of stem cells also in terms of genetic stability; (b) the reproducibility of beneficial effects; and (c) the safety of their use. Numerous studies have been conducted to understand the mechanisms that regulate ASC proliferation, growth and differentiation, however standard protocols about harvesting and processing techniques are not yet defined. It is also important to note that some steps in the procedures of harvesting and/or processing have been reported to affect recovery and/or the physiology of ASCs. Even considering the great opportunity that the ASCs provide for the identification of novel molecular targets for new or old drugs, the definition of homogeneous preparation methods that ensure adequate quality assurance and control, in accordance with current GMPs (good manufacturing practices), is required. Here, we summarize the literature reports to provide a detailed overview of the methodological issues underlying human ASCs isolation, processing, characterization, expansion, differentiation techniques, recalling at the same time their basilar principles, advantages and limits, in particular focusing on how these procedures could affect the ASC quality, functionality and plasticity
The emerging role of probiotics in neurodegenerative diseases: New hope for Parkinson's disease?
Get PDFNeurodegenerative disease etiology is still unclear, but different contributing factors, such as lifestyle and genetic factors are involved. Altered components of the gut could play a key role in the gut-brain axis, which is a bidirectional system between the central nervous system and the enteric nervous system. Variations in the composition of the gut microbiota and its function between healthy people and patients have been reported for a variety of human disorders comprising metabolic, autoimmune, cancer, and, notably, neurodegenerative disorders. Diet can alter the microbiota composition, affecting the gut-brain axis function. Different nutraceutical interventions have been devoted to normalizing gut microbiome dysbiosis and to improving biological outcomes in neurological conditions, including the use of probiotics. Preclinical and clinical investigations discussed in this review strengthen the correlation between intestinal microbiota and brain and the concept that modifying the microbiome composition may improve brain neurochemistry, modulating different pathways. This review will discuss the potential use of probiotics for Parkinson's disease prevention or treatment or as adjuvant therapy, confirming that gut microbiota modulation influences different pro-survival pathways. Future investigations in Parkinson's disease should consider the role of the gut-brain axis and additional comprehension of the underlying mechanisms is extremely necessary
Secretome of adipose tissue-derived stem cells (ASCs) as a novel trend in chronic non-healing wounds: An overview of experimental in vitro and in vivo studies and methodological variables
No full textWound healing is a complex process with a linear development that involves many actors in a multistep timeline commonly divided into four stages: Hemostasis, inflammation, proliferation, and remodeling. Chronic non-healing wounds fail to progress beyond the inflammatory phase, thus precluding the next steps and, ultimately, wound repair. Many intrinsic or extrinsic factors may contribute to such an occurrence, including patient health conditions, age-related diseases, metabolic deficiencies, advanced age, mechanical pressure, and infections. Great interest is being focused on the adipose tissue-derived stem cell’s (ASC) paracrine activity for its potential therapeutic impact on chronic non-healing wounds. In this review, we summarize the results of in vitro and in vivo experimental studies on the pro-wound healing effects of ASC-secretome and/or extracellular vesicles (EVs). To define an overall picture of the available literature data, experimental conditions and applied methodologies are described as well as the in vitro and in vivo models chosen in the reported studies. Even if a comparative analysis of the results obtained by the different groups is challenging due to the large variability of experimental conditions, the available findings are undoubtedly encouraging and fully support the use of cell-free therapies for the treatment of chronic non-healing wounds
Small bowel enterocyte apoptosis and proliferation are increased in the elderly
No full textBackground. It is known that in the elderly the small bowel does not reveal structural and functional deteriorations in normal conditions, whereas the absorptive function is impaired in stress conditions. Objective: The balance between enterocyte apoptosis and proliferation being responsible for the maintenance of tissue size, mucosal morphology and function in the gastrointestinal tract, the aim of our study was to evaluate the rates of enterocyte apoptosis and proliferation in the duodenal mucosa of aged human beings in comparison to adults. Methods: For this purpose, the terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick end labelling (TUNEL) technique and immunohistochemistry for MIB-1 detection were applied on histological sections of endoscopic duodenal biopsy specimens obtained from 12 healthy elderly subjects (mean age 77.6 years; M/F 7/5) and 12 healthy adult subjects (mean age 37.7 years; M/F 8/4). Counts were performed, at a constant magnification (x200), by computer-aided analysis and the results expressed as median percentages of positive enterocytes. Results: The results showed a significant increase in enterocyte apoptosis in the elderly (15.3 vs. 2.1% in the adults, p < 0.001) which was positively correlated (r(s) = 0.65, p < 0.05) with a significant increase in enterocyte proliferation (37.7 vs. 15.8% in the adults, p < 0.0001). Conclusions: These data suggest that the maintenance of mucosal architecture throughout the process of aging is due to either a hyperproliferative state or an exaggerated apoptosis with a consequent cellular immaturity, which may impair the absorptive function observed in stress conditions. Copyright (C) 2002 S. Karger AG, Basel
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