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A novel ets-2-related nuclear factor is involved in transcriptional activation of the human interleukin-12 p40 gene promoter in response to interferon-gamma and LPS stimulation of monocytic cells.
No full textA Novel ets-2-Related Nuclear Factor Is Involved in Transcriptional Activation of the Human Interleukin-12 p40 Gene Promoter in Response to Interferon- y and LPS Stimulation of Monocytic Cell
Mast cell within the microenvironment: Cellular and matrix cross-talk in physiopathological conditions
No full textMast cells are triggered to release histamine and other mediators of inflammation when immunoglobulin E (IgE) receptors on the cell membrane are brought into close proximity, i.e. aggregated. This is usually accomplished in model systems by crosslinking IgE-loaded receptors with multivalent ligands, but can also be achieved by monovalent ligands bound to a fluid lipid bilayer, which may be patterned or homogeneous. With homogeneous membranes, the receptors on the mast cell develop a spatial pattern that bears some similarity to the T cell synapse. Ligand presentation on membranes may be a good model for the interactions of mast cells with various parasites; thus, the development of spatial patterns of receptors and the consequence for mast cell signaling is likely to be important for this most basic mast cell role. In this chapter, we review the role of the spatial organization of signaling components and IgE receptors in mast cell signaling. © 2013 Nova Science Publishers, Inc. All rights reserved
Stem Cell Senescence as the Memory of Past Injuries
No full textStem cell senescence may play a central role in both aging and age-related pathologies, being associated with a functional impairment of both homeostasis and the regenerative properties of tissues. The possibility to interfere with this detrimental phenomenon requires a careful elucidation of the mechanisms that initiate and maintain this cellular response. In this review, we will discuss the hypothesis that cellular senescence could be considered the biological memory of the action of different types of stressors on the organism, leading to a complex phenotype that includes both intrinsic (e.g., gene expression, chromatin organization, and cell metabolism) and extrinsic (e.g., secretome) changes. Finally, it will be shown that cell senescence blunts the regenerative ability of human cardiac stem cells and that the pharmacological inhibition of this detrimental cell process restores the functional properties of primitive cells in vivo
Allergic responses and aryl hydrocarbon receptor novel pathway of mast cell activation.
No full textThe activation of the transcription factor aryl hydrocarbon receptor (AhR) is modulated by a wide variety of xenobiotics and ligands deriving from products of metabolism. The study of the contribution of AhR to allergic diseases has gained much interest in recent years. Here we discuss the role that environmental factors and metabolic products, particularly acting on AhR-expressing mast cells (MCs), could have in the development of local allergic/atopic response. Thus, this review will cover: a brief overview of the AhR mechanism of action in the immune system; a description of different AhR ligands and their effects to IgE-mediated MC activation in the allergic response, with particular attention to the role of IL-17; a discussion about the potential involvement of AhR in immune tolerance; and a conclusion on human diseases in which direct AhR activation of MC might have a major impact
Exploring a regulatory role for mast cells: 'MCregs'?
No full textRegulatory cells can mould the fate of the immune response by direct suppression of specific subsets of effector cells, or by redirecting effectors against invading pathogens and infected or neoplastic cells. These functions have been classically, although not exclusively, ascribed to different subsets of T cells. Recently, mast cells have been shown to regulate physiological and pathological immune responses, and thus to act at the interface between innate and adaptive immunity assuming different functions and behaviors at discrete stages of the immune response. Here, we focus on these poorly defined, and sometimes apparently conflicting, functions of mast cells
Synergistic regulation of the human interleukin-12 p40 promoter by NFkappaB and Ets transcription factors in Epstein-Barr virus-transformed B cells and macrophages.
No full textMonocytes/macrophages produce interleukin-12 (IL-12) in response to pathogenic stimulation, whereas most Epstein-Barr virus-transformed (EBV+) B cells constitutively secrete IL-12. The molecular mechanism regulating the constitutive IL-12 gene expression in EBV+ B cells has not been addressed. In this study, using the EBV+ B cell line RPMI-8866, we localized to the human IL-12 p40 promoter two essential cis elements, the NFkappaB site and the Ets site. The NFkappaB site was shown to interact with members of the NFkappaB family: p50 and c-Rel. The Ets site constitutively bound a multi-component Ets-2-containing complex. While the NFkappaB and Ets sites appear equally critical for inducible p40 promoter activity in macrophage cell lines, NFkappaB plays a more dominant role in the constitutive p40 promoter activity in EBV+ B cells. Transient expression of Ets-2 and c-Rel in B, T, and monocytic cell lines synergistically activated the IL-12 p40 promoter, apparently overcoming the requirement for cell type- or stimulant-specific transcription factors. These data provide new evidence that full activation of the human IL-12 p40 promoter may result primarily from the interplay between NFkappaB and Ets family members
The positive impact of virtual microscopy on histopathology education: a comparative, student-centered study
Get PDFBecause of the recent pandemic, new teaching methods have been trialed, even in traditional disciplines such as histopathology that typically involve extensive hands-on laboratory work. In this study, we investigated the effects of three different learning modalities in histopathology teaching: optical microscopy, in-class virtual microscopy (VM), and online VM lectures. We examined relational aspects, didactic effectiveness, and satisfaction in these learning settings, both during class time and in private study, outside the dedicated spaces and hours of the university. The comparative design of the study, based on a set of surveys taken during the course and at its end, resulted in valuable methodological insights and a clear picture of the students' needs. These were characterized both by high technological expectations and by a desire for a stimulating social environment. Our results show that the implementation of new learning tools has a positive impact on teaching, and not only at the didactic level. It also positively affects the way the university is experienced by the students, it facilitates their desired socializing lifestyles, and it exposes them, as a new generation of professionals, to the latest technologies used by specialty physicians.NEW & NOTEWORTHY Our study examines the didactical impact and perceived value of distance learning and virtual microscopy (VM) teaching among students in histopathology laboratories and at home. To our knowledge, this is the first study investigating such issues in the postpandemic setting. These novel teaching methods complement the innovative technologies currently used in diagnostic medicine
Identification and characterization of a novel Ets-2-related nuclear complex implicated in the activation of the human interleukin-12 p40 gene promoter.
No full textInterleukin-12 (IL-12) is a proinflammatory cytokine produced by antigen-presenting cells in response to many microbial infections. IL-12 plays an important role in the generation of T helper type-1 cells, which favor cell-mediated immune response. IL-12 is composed of two different subunits, p40 and p35, whose expression can be regulated concomitantly or differentially. Monocytic cells, the major producers of IL-12, can be primed by interferon-gamma (IFN-gamma) to produce optimal amounts of IL-12 in response to LPS stimulation as a consequence of bacterial infection. The priming effect is exerted primarily at the transcriptional level on the p40 promoter in conjunction with the effects of LPS, possibly by inducing specific transcription factors, which individually have no direct effect but which cooperatively can activate the promoter. We examined in detail one of these DNA-protein interactions observed around an Ets-2 element situated at -211/-207 of the p40 promoter, which is known to be a functionally critical site. This region interacts with a nuclear complex termed F1 that appears to be highly inducible by either IFN-gamma treatment for 16 h or lipopolysaccharide stimulation for 8 h. F1 binding to the Ets-2 site requires a considerable amount of spacing around the Ets-2 site, as revealed by gel mobility shift and in vitro methylation assays. Supershift experiments and DNA affinity purification indicated that both Ets-2 and a novel, antigenically related protein with an approximate molecular mass of 109 kDa are part of the F1 complex, together with additional components including IRF-1 and c-Rel. This novel protein is designated GLp109 for its inducibility by IFN-gamma or lipopolysaccharide. Its possible role in the activation of the IL-12 p40 promoter is discussed
Positive and negative regulation of interleukin-12 gene expression.
No full textInterleukin-12 (IL-12) is a pivotal cytokine representing the link between the cellular and humoral branches of an effective host immune defense apparatus. IL-12 is a heterodimer produced by phagocytic, B, dendritic, and possibly other accessory cells in both innate and adaptive immune responses. It is a key factor in the induction of T cell-dependent and independent activation of macrophages, generation of T helper type 1 (Th1) and cytotoxic T cells, suppression of IgG1 and IgE production, induction of organ-specific autoimmunity, and resistance to bacterial and parasitic infections [1]. IL-12 has a powerful anti-tumor and anti-metastatic activity against many murine tumors [2-5] as well as human tumors [6-17]. The genes encoding the two heterologous chains of IL-12, p40 and p35 are located on different human chromosomes. Together, p40 and p35 form the biologically active IL-12. Their expressions are highly coordinated during an effective immune response. However, under some pathological conditions, IL-12 is under- or overexpressed, resulting either in a lack of resistance to microbial infection and to uncontrolled tumor growth, or in destructive inflammation, respectively. A transient or irreversible dysregulation of IL-12 production may reflect a pathogen/tumor cell-induced disruption in the highly coordinated expression of p40 and p35. The understanding of the molecular mechanisms governing the expression of IL-12 p40 and p35 genes in the context of interactions between pathogens and the immune system is essential in efforts aimed at designing therapeutic strategies to treat infectious and malignant diseases
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