Checconi P.,University of Rome La Sapienza |
Salzano S.,Brighton and Sussex Medical School |
Bowler L.,University of Brighton |
Mullen L.,Brighton and Sussex Medical School |
And 10 more authors.
PLoS ONE | Year: 2015
Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-αrelease, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions. © 2015 Checconi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Civitelli L.,University of Rome La Sapienza |
Civitelli L.,Linkoping University |
Marcocci M.E.,University of Rome La Sapienza |
Celestino I.,University of Rome La Sapienza |
And 5 more authors.
Journal of NeuroVirology | Year: 2015
Several data indicate that neuronal infection with herpes simplex virus type 1 (HSV-1) causes biochemical alterations reminiscent of Alzheimer’s disease (AD) phenotype. They include accumulation of amyloid-β (Aβ), which originates from the cleavage of amyloid precursor protein (APP), and hyperphosphorylation of tau protein, which leads to neurofibrillary tangle deposition. HSV-1 infection triggers APP processing and drives the production of several fragments including APP intracellular domain (AICD) that exerts transactivating properties. Herein, we analyzed the production and intracellular localization of AICD following HSV-1 infection in neurons. We also checked whether AICD induced the transcription of two target genes, neprilysin (nep) and glycogen synthase kinase 3β (gsk3β), whose products play a role in Aβ clearance and tau phosphorylation, respectively. Our data indicate that HSV-1 led to the accumulation and nuclear translocation of AICD in neurons. Moreover, results from chromatin immunoprecipitation assay showed that AICD binds the promoter region of both nep and gsk3β. Time course analysis of NEP and GSK3β expression at both mRNA and protein levels demonstrated that they are differently modulated during infection. NEP expression and enzymatic activity were initially stimulated but, with the progression of infection, they were down-regulated. In contrast, GSK3β expression remained nearly unchanged, but the analysis of its phosphorylation suggests that it was inactivated only at later stages of HSV-1 infection. Thus, our data demonstrate that HSV-1 infection induces early upstream events in the cell that may eventually lead to Aβ deposition and tau hyperphosphorylation and further suggest HSV-1 as a possible risk factor for AD. © 2015, Journal of NeuroVirology, Inc.
Sgarbanti R.,Telematic University |
Amatore D.,Advanced Biotechnology Incubator |
Amatore D.,University of Rome La Sapienza |
Celestino I.,Advanced Biotechnology Incubator |
And 11 more authors.
Current Topics in Medicinal Chemistry | Year: 2014
Influenza virus infections represent a big issue for public health since effective treatments are still lacking. In particular, the emergence of strains resistant to drugs limits the effectiveness of anti-influenza agents. For this reason, many efforts have been dedicated to the identification of new therapeutic strategies aimed at targeting the virus-host cell interactions. Oxidative stress is a characteristic of some viral infections including influenza. Because antioxidants defend cells from damage caused by reactive oxygen species induced by different stimuli including pathogens, they represent interesting molecules to fight infectious diseases. However, most of the available studies have found that these would-be panaceas could actually exacerbate the diseases they claim to prevent, and have thus revealed "the dark side" of these molecules. This review article discusses the latest opportunities and drawbacks of the antioxidants used in anti-influenza therapy and new perspectives. © 2014 Bentham Science Publishers.
Botta G.,University of Tuscia |
Bizzarri B.M.,University of Tuscia |
Garozzo A.,University of Catania |
Timpanaro R.,University of Catania |
And 7 more authors.
Bioorganic and Medicinal Chemistry | Year: 2015
Hydroxytyrosol and dihydrocaffeoyl catechols with lipophilic properties have been synthesized in high yield using tyrosinase immobilized on multi-walled carbon nanotubes by the Layer-by-Layer technique. All synthesized catechols were evaluated against a large panel of DNA and RNA viruses, including Poliovirus type 1, Echovirus type 9, Herpes simplex virus type 1 (HSV-1), Herpes simplex virus type 2 (HSV-2), Coxsackievirus type B3 (Cox B3), Adenovirus type 2 and type 5 and Cytomegalovirus (CMV). A significant antiviral activity was observed in the inhibition of HSV-1, HSV-2, Cox B3 and CMV. The mechanism of action of the most active dihydrocaffeoyl derivative was investigated against a model of HSV-1 infection. © 2015.
Aleandri M.,University of Rome La Sapienza |
Conte M.P.,University of Rome La Sapienza |
Simonetti G.,University of Rome La Sapienza |
Panella S.,University of Rome La Sapienza |
And 12 more authors.
PLoS ONE | Year: 2015
Modifications of intestinal glycoreceptors expression, in particular CEACAM6, typically found in ileal Crohn's disease (CD), favor, among the commensal species of microbiota, the enrichment in Escherichia coli. Removal of protein glycosidic residues by neuraminidase, a sialidase typical of influenza virus, increases adhesion ability of Escherichia coli to Caco-2 intestinal cells. In this study we investigated whether influenza virus infection of human intestinal epithelial cells could influence the adhesiveness of different Escherichia coli strains isolated from CD patients by altering surface glycoreceptors. Influenza virus infection of intestinal cells increased exposure of galactose and mannose residues on the cell surface. In particular, glycoreceptors Thomsen-Friedenreich and CEACAM6 were over-expressed in influenza virus infected cells. In the same experimental conditions, a significant increase in bacterial adhesiveness was observed, independently of their own adhesive ability. The increase was reverted by treatment with anti-TF and anti-CEACAM6 antibodies. Interestingly, influenza virus was able to efficiently replicate in human primary intestinal cells leading to TF exposure. Finally, intestinal infected cells produced high levels of pro-inflammatory cytokines compared to control. Overall these data suggest that influenza virus infection, could constitute an additional risk factor in CD patients. © 2015 Aleandri et al.