1,721,313 research outputs found

    Role of inflammatory mediators in angiogenesis

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    The angiogenic process involves several cell types and mediators, which interact to establish a specific microenvironment suitable for the formation of new capillaries from pre-existing vessels. Angiogenesis occurs in several physiological and pathological conditions, such as embryo development and wound healing, diabetic retinopathy and tumours. Inflammatory cells, namely monocytes/macrophages, T lymphocytes and neutrophils, fully participate in the angiogenic process by secreting cytokines that may affect endothelial cell (EC) functions, including EC proliferation, migration and activation. Angiogenesis is the result of a net balance between the activities exerted by positive and negative regulators. With regards to inflammatory cells and endothelium cross-talk, such balance is conceptually very similar to that of pro-inflammatory and anti-inflammatory mediators that modulate an appropriate inflammatory response. In this review we will mainly discuss the relevance of both physiological and pathological inflammatory processes in angiogenesis, with particular regards to microenvironmental contribution. We will also describe some of the most relevant pro-inflammatory cytokines in the modulation of the angiogenic process. Furthermore, we will concentrate on what has been recently reported about the mechanism by which some of these cytokines are induced during inflammation to promote a suitable microenvironment for angiogenesis and tumour progression. Pro-angiogenic cytokines, such as IL-1 and TNF, and anti-angiogenic cytokines such as IFN-gamma and IL-12, will be briefly described. We will try to provide a rationale for the use of both cytokines and cytokine blockades as novel potential pharmaceutical targets to modulate angiogenesis in chronic inflammation as well as in cancer

    Nelle viscere della montagna. Paesaggi pre-industriali sulla dorsale Agno-leogra

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    Questo articolo illustra una parte dei risultati ottenuti nelle campagne svolte sulla dorsale Agno-Leogra (Vicenza) negli anni 2011-2012, limitatamente al tematismo minerario e nel particolare solo i dati relativi al versante orientale della dorsale2. Il lavoro non pretende dunque di essere esaustivo, ma di dare conto di risultati assai significativi, oltre che in termini scientifici, in termini di valorizzazione di quest’area prealpina, nella riscoperta di quello che era un antico paesaggio minerario risalente ad età precedenti la rivoluzione industriale

    Effects of hypoxia on the antiproliferative activity of human interferons

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    We studied the effects of pharmacologically attainable concentrations of interferon-alpha (IFN-alpha) and gamma (IFN-gamma) on the growth of cells incubated under hypoxic conditions (2% O2; approximately 14 mm Hg partial pressure) or exposed to oxygen at atmospheric pressure (21% O2; approximately 147 mm Hg). The cells were from four IFN-sensitive lines: A-549 lung carcinoma and G-361 human melanoma cells grow better under hypoxic conditions, but the growth of Hep-2 laryngeal carcinoma and WISH amnion cells is not affected by the environmental oxygen tension. The antiproliferative effects of the IFN were assessed in terms of cell cloning efficiency and also from the number of cells, relative to controls, measured 1, 2, and 3 days after seeding. Under hypoxic conditions, the cloning efficiency of A-549 and G-361 cells was increased, and they became significantly less responsive to the antiproliferative effect of IFN, and especially of IFN-gamma. No such effects were seen with WISH or Hep-2 cells. Hypoxic conditions are found in the necrotic areas present in most solid tumors, and our results suggest that these may decrease the antiproliferative effects of IFN. They may in part explain why IFNs have so little antitumor activity in such tumors, and they also suggest methods that may increase this activity

    Hypoxia induces the expression and release of interleukin 1 receptor antagonist in mitogen-activated mononuclear cells

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    Hypoxia modulates the expression of inflammatory mediators in a variety of cell types. Since interleukin (IL-)1 receptor antagonist (Ra) is a cytokine widely associated with an inflammatory state and is expressed by activated mononuclear cells, we investigated whether hypoxia induces IL-1Ra expression in human peripheral blood mononuclear cells (PBMC) activated by phytohaemagglutinin (PHA). RNase protection assay, conducted on PHA-activated PBMC cultured under hypoxic conditions (2% O(2)) for 16-40 h, revealed that hypoxia enhances IL-1Ra mRNA expression. Further, IL-1Ra release was significantly affected by hypoxia, as determined by ELISA. Concomitantly, hypoxia enhanced, even though at a lesser extent, both IL-1alpha and IL-1beta mRNA expression and release, as determined by RPA and ELISA. However, at 40 h of treatment, hypoxia did not affect cell viability and DNA fragmentation, but caused an inhibition of the proliferation index after PHA stimulation, obtained by MTT assay. These results suggest that activated mononuclear cells tend to respond to hypoxic stress by modulating the expression of IL-1Ra and IL-1-related molecules and their release in the surrounding microenvironment
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