1,721,061 research outputs found
HSV-1 induces macrophage activation and dysregulation in monocytes
No full textClinical cases of double infections by fungi and viruses are increasing, especially in immunocompromised hosts. To date, the biomolecular events that characterize the outcome of polymicrobic diseases remain poorly investigated and little is known on the mutual interactions occurring between pathogens. In order to investigate the interplay between microrganisms co-infecting macrophagic cells, we recently set up an in vitro model in which a monocytic cell line was infected with human herpesvirus 6 and C. neoformans. In the present work, we used an similar model to understand the molecular mechanisms underlying interactions between herpes simplex virus 1 (HSV-1) and C. albicans. The monocytic cell line THP-1 was infected with HSV-1 and, after an overnight incubation, cells were exposed to C. albicans. The cell response to the viral infection was evaluated as phagocytosis of C. albicans and killing of the ingested fungus. Moreover, a number of activation markers (CD38, CD69, CD95) and adhesion molecules (CD54, TLR-2, CD11b, CD106) was evaluated by FACS analysis in THP-1 cells. THP-1 cells infected with HSV-1 showed increased phagocytosis of C. albicans but reduced killing capability, suggesting that in the course of a double infection macrophages could contribute to yeast dissemination. Activation markers (CD38 and CD69) were found down expressed by FACS analysis in HSV-1-infected THP-1 cells, accounting for the failure in the antifungal activity
Nuclear redox control of stem cell ageing
No full textMesenchymal stem cells (MSCs) have emerged as an important tool that can be used for drug screening, disease
modeling and tissue regeneration thanks to their easy preparation, differentiation potential and immunomodulatory
activity.
A redox imbalance, due to extensive culture of stem cells in vitro prior to clinical use, can lead to oxidative stress.
However, oxidative stress is known to play an important role in modulating different stem cells properties, such as
self-renewal, proliferation, differentiation and senescence. A specific source of reactive oxygen species, the NADPH
oxidase isoform 4 (Nox4), can localize also into the nuclei where it can have an impact on the regulation of crucial
stemness-related genes. Moreover, the accumulation in human MSCs’ nuclei of the nuclear lamina precursor,
prelamin A, gives rise to a premature aging phenotype that ultimately causes reduced functionality of these cells in
vivo.
The aim of the study was to investigate the aging process occurring during in vitro expansion of human fetal
MSCs, obtained from amniotic fluid at similar gestational age. This process is certainly influenced by the oxidative
stress exposure implied in extensive culture, but could be also donor dependent. The analysis of 15 AFSC samples
allowed to classify them in groups with different levels of stemness properties evident even since the first passages
in culture. In summary, the expression of Oct-4, a pluripotency gene, and proliferation rate are inversely correlated
to the presence of the nuclear form of Nox4, the content of reactive oxygen species, DNA damage signs and the
onset of senescence and premature aging markers, including accumulation of prelamin A, p21 and p16. Indeed,
coimmunoprecipitation experiments demonstrated an interaction between prelamin A and Nox4, suggesting an
interplay of these proteins in modulating the maintenance of stemness properties
Beretti F., Cermelli C., Cenacchi V., Orsi C., Blasi E., Portolani M.
No full textMicroglia activation occurs during brain injury, ischemia and several neurological disorders. Moreover, microglial cells are highly dynamic structures also during the “resting” state in vivo, releasing neurotrophic factors and/or pro- and anti-inflammatory cytokines. Recently, we obtained a transmissible cytotoxic activity (TCA) from the cerebrospinal fluid of a patient with brain ischemia. We demonstrated that this TCA is associated with one or 2 protein(s), that supposedly underwent misfolding, and causes apoptotic cytotoxicity in a variety of cell lines. In this work, we studied microglia response to this TCA. The murine brain macrophage cell line RR4 was stimulated with TCA. Its response was evaluated as phagocytosis and antifungal activity against C. Albicans, and as secretion pattern, measuring MIP-1and TNF- by commercial sandwich ELISAs, nitric oxide (NO) by Griess reaction and phosphorylation of p38 by Fast Activated Cell-based ELISA.Microglia stimulated with TCA showed an increase in phagocytosis of C. albicans. On the contrary, the macrophage capability to kill the ingested fungi was diminished. The analysis of soluble factors secreted by microglial cells in response to TCA demonstrated an increase in MIP-1TNF- NO and an activation of p38 MAP kinase. These results suggest an initial microglia activation induced by TCA leading to an increase in candida ingestion not followed by killing of the fungus. Activation of p38 MAP kinase could suggest the induction of a signaling cascade leading to TCA production which in turn could cause failure in the antifungal activity. Moreover, MIP-1a, NO and TNF-a secretion by microglia cells and induction of apoptosis could provide an in vitro model for the cell events associated with brain ischemia
Antiviral activity of propolis
No full textPropolis, a natural product of beehives, comprises a complex of chemicals, the most important being flavonoids, which are known to havw antiviral activities. Alcohol solutions of 5 different commercial products were tested in vitro against HSV-1, CoxB5, Adenovirus, Mumps virus.All the propolis preparations under study showed antiviral activity against at least some of the virus tested, although with different efficacy
Search for viruses in the CSF of patients with acute neurological disorders: possible involvement of beta-and gamma-herpesviruses
No full textIn the years 1999-2001, 868 samples of cerebrospinal fluid (CSF) from as many patients with acute neurological manifestations of suspected viral origin were analysed for the presence of viruses at the Centre for the Diagnosis of Viral Diseases of the University of Modena and Reggio Emilia. Neurological patients included 788 immunocompetent subjects and 80 patients with impaired immunity due to human immunodeficiency virus (HIV) seropositivity. Of the CSF samples, 125 (15.8%) were positive for one or more viruses among the immunocompetent patients, whereas 33 (41.1%) were positive among the HIV cohort. DNA and RNA viruses were detected in the first group of CSF samples whereas only DNA viruses were found in the second group. In immunocompetent patients the frequency of enteroviruses prevailed over that of other RNA virus families (p = 0.001) and that of herpesviruses over the frequency of other DNA virus families (p = 0.001). Among herpesvirus members, the Epstein-Barr gamma-herpesvirus prevailed on alpha-herpesviruses in each of the two groups of patients (p = 0.05 in the immunocompetent group and p = 0.006 in HIV-positive patients). The clinical relevance both of this virus and of beta-herpesviruses as a cause of neurological disorders is discussed
Role of hepatocyte growth factor in the immunomodulation potential of amniotic fluid stem cells
Full text linkHuman amniotic fluid stem cells (hAFSCs) may be useful for regenerative medicine because of their potential to differentiate into all three germ layers and to modulate immune response with different types of secretion molecules. This last issue has not been completely elucidated. The aim of this study was to investigate the secretome profile of the hAFSC, focusing on the role of hepatocyte growth factor (HGF) in immunoregulation through short and long cocultures with human peripheral blood mononuclear cells. We found that HGF produced by hAFSCs exerts a cytoprotective role, inducing an increase in caspase-dependent apoptosis in human immune cells. This study provides evidence supporting the hypothesis that amniotic fluid is an ideal source of stem cells for expansion and banking properties for therapeutic use. hAFSCs not only are less immunogenic but also can secrete immunoregulatory factors that may be useful in autoimmune diseases or allogenic implants.
SIGNIFICANCE:
New information about the secretome pattern is reported in this paper. Human amniotic fluid stem cells (hAFSCs) possess immunomodulatory properties involving hepatocyte growth factor production. hAFSCs could be used in immunotherapies and might be able to avoid allogenic rejectio
Post-mortem diagnosis of encephalitis in a 75-year-old man associated with human herpesvirus-6 variant A
No full textAbstract An HHV-6 variant A infection is described in a 75 year-old man in association with meningoencephalitis identified at autopsy. The patient presented with fever and anorexia, then he developed altered consciousness, motor weakness, progressive lethargy, and coma, and died 21 days after hospital admission. Histopathological examination showed perivascular lymphocytic infiltrates in the central nervous system (CNS). Serum and cerebral spinal fluid (CSF) samples drawn from the patient were tested for viruses by a nested polymerase chain reaction (nPCR). HHV-6 primers A and C [Aubin et al., [1991]: J Clin Microb 29: 367-372] and HS6AE and HS6AF from [Dewhurst et al. ([1993]): J Clin Microb 31: 416-418] disclosed a 750 bp genomic product of HHV-6 in both types of biological samples. Restricted site analysis showed that the HHV-6 DNA amplified belonged to the variant A of the virus. Short sequences of HHV-6 DNA could also be detected in the DNA extracted from formalin-fixed, paraffin-embedded sections of CNS tissues by use of one (GM5 and GM6) of three pairs of HHV-6 primers that were selected. Immunohistochemical examination of brain sections, employing a specific monoclonal antibody directed against the HHV-6 gp 102 protein, detected the viral antigen in neurons and glial cells. J. Med. Virol. 77:244-248, 2005. © 2005 Wiley-Liss, Inc
Human herpesvirus 8 DNA in the cerebrospinal fluid of a patient with sensory impairment
No full textThis note reports the finding of human herpes virus 8 DNA in the cerebrospinal fluid of a woman with sensory impairment correlated with a basal disease suspected to be multiple sclerosis
Neutralization by human serum samples of a transmissible agent isolated from the cerebrospinal fluid of neurological patients.
No full textA transmissible cytotoxic agent thought to be associated with one or more misfolded protein(s) was found in severalcerebrospinal fluid (CSF) samples from neurological patients. Since some experiments carried out to identify this unusualinfectious factor showed the block of its propagation by rabbit gammaglobulins (IgGs), the search for such anactivity by human IgGs was programmed. Neutralizing assays carried out using human sera as IgGs source showeda blocking property displayed by: twenty serum samples from as many patients with a diagnosis of acute infection,two of ten sera from healthy subjects and four serum samples from patients with lupus erythematous (SLE). Whenneutralizing sera were tested on cell cultures in immunofluorescence assays for the serum ability to label specific protein(s), similar fluorescent pictures resulted in treated and control cells. On the other hand, the SLE serum samplesdisclosed a granulosity of the nuclear material of cytotoxic cells in accordance with the DNA apoptotic laddering reportedin previous papers. Oxidative disorders, as suggested by the immunoblotting analysis of the antioxidant enzymesMn-superoxide dismutase (SOD2) and heme-oxygenase 1 (HO-1), point to an alteration of the oxidative pathwayamong the causes of the DNA damage induced by the cytotoxic transmissible agent under study
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