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Roberto P Garofalo - One of the best experts on this subject based on the ideXlab platform.

  • respiratory syncytial virus induces nrf2 degradation through a promyelocytic leukemia protein ring finger protein 4 dependent pathway
    Free Radical Biology and Medicine, 2017
    Co-Authors: Narayana Komaravelli, Maria Ansar, Roberto P Garofalo, Antonella Casola
    Abstract:

    Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or specific treatments are available. RSV causes airway Mucosa Inflammation and cellular oxidative damage by triggering production of reactive oxygen species and by inhibiting at the same time expression of antioxidant enzymes, via degradation of the transcription factor NF-E2-related factor 2 (NRF2). RSV infection induces NRF2 deacetylation, ubiquitination, and degradation through a proteasome-dependent pathway. Although degradation via KEAP1 is the most common mechanism, silencing KEAP1 expression did not rescue NRF2 levels during RSV infection. We found that RSV-induced NRF2 degradation occurs in an SUMO-specific E3 ubiquitin ligase - RING finger protein 4 (RNF4)-dependent manner. NRF2 is progressively SUMOylated in RSV infection and either blocking SUMOylation or silencing RNF4 expression rescued both NRF2 nuclear levels and transcriptional activity. RNF4 associates with promyelocytic leukemia - nuclear bodies (PML-NBs). RSV infection induces the expression of PML and PML-NBs formation in an interferon (INF)-dependent manner and also induces NRF2 - PMN-NBs association. Inhibition of PML-NB formation by blocking IFN pathway or silencing PML expression resulted in a significant reduction of RSV-associated NRF2 degradation and increased antioxidant enzyme expression, identifying the RNF4-PML pathway as a key regulator of antioxidant defenses in the course of viral infection.

  • perflubron reduces lung Inflammation in respiratory syncytial virus infection by inhibiting chemokine expression and nuclear factor κb activation
    American Journal of Respiratory and Critical Care Medicine, 2002
    Co-Authors: Helene A Haeberle, Frances Nesti, Hans Juergen Dieterich, Zoran Gatalica, Roberto P Garofalo
    Abstract:

    Airway Mucosa Inflammation plays a critical role in the pathogenesis of lower respiratory tract infections caused by respiratory syncytial virus (RSV), the major etiologic agent of bronchiolitis in infancy. Type and intensity of cellular infiltration are dictated by inflammatory chemokines, which are rapidly and abundantly induced in lung tissue by RSV. This process is, to a large extent, transcriptionally regulated by RSV-mediated activation of the nuclear factor–κB. The administration of a perfluorocarbon (PFC) liquid, such as perflubron, during partial liquid ventilation improves lung function and also reduces Inflammation. In this study we demonstrate that treatment of BALB/c mice with perflubron intranasally 6 hours after RSV infection significantly inhibited lung cellular Inflammation as well as the expression of the chemokines RANTES, MIP-1α, MIP-1β, and MIP-2, compared with phosphate-buffered saline–treated control mice. However, perflubron treatment did not affect RSV replication. Strikingly, tre...

Junqiu Luo - One of the best experts on this subject based on the ideXlab platform.

  • chlorogenic acid improves intestinal barrier functions by suppressing Mucosa Inflammation and improving antioxidant capacity in weaned pigs
    Journal of Nutritional Biochemistry, 2018
    Co-Authors: Jiali Chen, Daiwen Chen, Xiangbing Mao, Ping Zheng, Zhiqing Huang, Junqiu Luo
    Abstract:

    Intestinal barrier plays key roles in maintaining intestinal homeostasis. Inflammation and oxidative damage can severely destroy the intestinal integrity of mammals. Chlorogenic acid (CGA) is a natural polyphenol present in human diet and plants, possessing potent antioxidant and anti-inflammatory activities. This study was conducted to investigate the protective effects of CGA and its molecular mechanisms on intestinal barrier function in a porcine model. Twenty-four weaned pigs were allotted to two groups and fed with a basal diet or a basal diet containing 1000 mg/kg CGA. The results showed that CGA decreased serum D-lactate and diamine oxidase levels, and enhanced the expression and localization of claudin-1 protein in apical intercellular region of small intestinal epithelium. Interestingly, CGA significantly decreased the Mucosa histamine and tryptase contents, as well as the tryptase-positive mast cell counts. Moreover, the expression levels of critical Inflammation molecules (interleukin-1β, interleukin-6, tumor necrosis factor-α, and nuclear factor-κB) were down-regulated by CGA in jejunal and ileal Mucosa. However, the expression levels of Inflammation repressors (suppressor of cytokine signaling 1 and toll-interacting protein) were up-regulated by CGA. Importantly, CGA decreased the malondialdehyde content but elevated glutathione peroxidase and catalase content in duodenal and jejunal Mucosa. The expression levels of critical molecules in antioxidant signaling (nuclear factor erythroid-derived 2-related factor 2 and heme oxygenase-1) were elevated by CGA in duodenal and jejunal Mucosa. These results suggested that CGA could ameliorate intestinal barrier disruption in weaned pigs, which might be mediated by suppressing the TLR4/NF-κB signaling pathway and activating the Nrf2/HO-1 signaling pathway.

  • chlorogenic acid improves intestinal development via suppressing Mucosa Inflammation and cell apoptosis in weaned pigs
    ACS omega, 2018
    Co-Authors: Jiali Chen, Hongmei Xie, Daiwen Chen, Xiangbing Mao, Ping Zheng, Yuheng Luo, Junqiu Luo
    Abstract:

    Chlorogenic acid (CGA) is a naturally occurring polyphenol in the human diet and plants, exhibiting antioxidant and anti-inflammatory activities. This study was conducted to investigate the effects of CGA on intestinal development and health in weaned pigs. Twenty-four weaned pigs were randomly assigned to two treatments and fed with a basal diet or a basal diet supplemented with 1000 mg/kg CGA. After a 14 d trial, samples were collected. Compared with the control group, CGA supplementation decreased the serum tumor necrosis factor-α, interleukin-6, and interleukin-1βIL-6 concentrations and elevated the serum immunoglobulin G and jejunal secretory immunoglobulin A concentrations. Meanwhile, jejunal villus height, duodenal and jejunal villus width, and jejunal and ileal villus height/crypt depth were increased by CGA. CGA not only decreased the number of duodenal and jejunal cells in the G0G1 phase but also increased the number of jejunal and ileal cells in the S phase. The percentages of late and total apoptotic cells in jejunum and the ratio of B-cell lymphoma-2-assiciated X protein to B-cell lymphoma-2 (Bcl-2) in duodenum and jejunum were also decreased by CGA supplementation. Finally, CGA upregulated the expression level of Bcl-2 in duodenum and jejunum, whereas it downregulated the expression levels of caspase-3 in duodenum and jejunum, caspase-9 in jejunum, as well as Fas in jejunum and ileum. This study suggested that the beneficial effects of CGA on intestinal development and health are partially due to improvement in immune defense and suppression in excessive apoptosis of intestinal epithelial cells in weaned pigs.

Riccardo Troncone - One of the best experts on this subject based on the ideXlab platform.

  • faecal calprotectin as reliable non invasive marker to assess the severity of Mucosal Inflammation in children with inflammatory bowel disease
    Digestive and Liver Disease, 2008
    Co-Authors: Berni R Canani, Gianluca Terrin, L Rapacciuolo, Erasmo Miele, M C Siani, C Puzone, L Cosenza, Annamaria Staiano, Riccardo Troncone
    Abstract:

    Background. An accurate monitoring of Mucosal Inflammation is important for an effective management of patients with inflammatory bowel disease. Intestinal Inflammation can be detected by faecal calprotectin level determination. Aim. To comparatively evaluate the accuracy of faecal calprotectin, clinical scores, common serum markers and endoscopy in the assessment of the severity of intestinal Mucosa Inflammation in children with inflammatory bowel disease. Methods. Fifty-eight paediatric patients (mean age 13.9 years, 95% CI 2.9–14.8; male 28) with confirmed inflammatory bowel disease (26 Crohn’s disease, 32 ulcerative colitis) were enrolled. Before endoscopy, all patients underwent a complete evaluation including: clinical scores, erythrocyte sedimentation rate, C-reactive protein and faecal calprotectin determination. The severity of Mucosal Inflammation was assessed using specific endoscopic and histologic scores. Results. Faecal calprotectin showed a high correlation (r = 0.655) with the histologic grade of Mucosal Inflammation, similar to that observed for endoscopy (r = 0.699), and it resulted the most accurate tool (sensitivity 94%, specificity 64%, positive predictive value 81%, negative predictive value 87%) to detect the presence of active Mucosal Inflammation when compared to clinical scores and common serum markers. In patients with apparent clinical and laboratory remission the accuracy of faecal calprotectin resulted further improved (sensitivity 100%, specificity 80%, positive predictive value 67%, negative predictive value 100%). Conclusions. A more accurate assessment of the severity of Mucosal Inflammation can be achieved by the determination of faecal calprotectin levels compared to other common clinical and laboratory indices. This non-invasive and objective method could be particular useful in patients with apparent clinical and laboratory remission. © 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  • diagnostic value of faecal calprotectin in paediatric gastroenterology clinical practice
    Digestive and Liver Disease, 2004
    Co-Authors: Berni R Canani, Gianluca Terrin, L Rapacciuolo, M Romano, Tanturri L De Horatio, Francesco Manguso, Pia Cirillo, F Paparo, Riccardo Troncone
    Abstract:

    Abstract Background. Faecal calprotectin (FC) is a new marker of intestinal Inflammation. Data on FC in paediatric gastroenterology clinical practice are still scarce. Aims. To assess FC values in different paediatric gastrointestinal diseases comparing them with those obtained in healthy children. Patients. Two hundred and eighty-one children (age range 13–216 months) consecutively referred for gastrointestinal symptoms. Seventy-six healthy controls (age range 13–209 months). The exclusion criteria in healthy children were the following: any known underlying chronic disease or a history of abdominal pain, diarrhoea, acute respiratory tract infection, intake of non-steroidal anti-inflammatory drugs, gastric acidity inhibitors, antibiotics, drugs influencing gut motility, and menstrual or nasal bleeding in the last 3 weeks. Methods. Stool samples stored, prepared and analyzed by an ELISA assay. Results. In healthy children the median FC value was 28.0 μg/g (15–57 interquartile range) with a 95th percentile value of 95.3 μg/g. An increase in FC concentration was observed in all diseases characterized by gastrointestinal Mucosa Inflammation, and the active inflammatory bowel disease patients showed the higher FC values. All children affected by functional bowel disorders or by non-inflammatory diseases showed normal values. We calculated an optimized FC cut off value of 102.9266 μg/g (revealed by the receiver operating characteristic curve) to distinguish patients with active organic/inflammatory disorders from healthy subjects and from patients with functional bowel disorders. Conclusions. Calprotectin is a sensitive, but not disease specific, marker to easily detect Inflammation throughout the whole gastrointestinal tract. It may help in identifying an organic disease characterized by intestinal Mucosa Inflammation and in the differential diagnosis of functional bowel disorders.

Dieter Jungst - One of the best experts on this subject based on the ideXlab platform.

Saoirse E Osullivan - One of the best experts on this subject based on the ideXlab platform.

  • palmitoylethanolamide and cannabidiol prevent Inflammation induced hyperpermeability of the human gut in vitro and in vivo a randomized placebo controlled double blind controlled trial
    Inflammatory Bowel Diseases, 2019
    Co-Authors: D G Couch, Hollie Cook, Catherine A Ortori, Dave Barrett, Jonathan N Lund, Saoirse E Osullivan
    Abstract:

    Background and aims We aimed to examine, for the first time, the effect of cannabidiol (CBD) and palmitoylethanolamide (PEA) on the permeability of the human gastrointestinal tract in vitro, ex vivo, and in vivo. Methods Flux measurements of fluorescein-labeled dextrans 10 (FD10) and fluorescein-labeled dextrans 4 (FD4) dextran across Caco-2 cultures treated for 24 hours with interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα) (10 ng·mL−1) were measured, with or without the presence of CBD and PEA. Mechanisms were investigated using cannabinoid receptor 1 (CB1), cannabinoid receptor 2 (CB2), transient receptor potential vanilloid 1 (TRPV1), and proliferator activated receptors (PPAR) antagonists and protein kinase A (PKA), nitric oxide synthase, phosphoinositide 3-kinases, extracellular signal–regulated kinases (MEK/ERK), adenylyl cyclase, and protein kinase C (PKC) inhibitors. Human colonic Mucosal samples collected from bowel resections were treated as previously stated. The receptors TRPV1, PPARα, PPARδ, PPARγ, CB1, CB2, G-coupled protein receptor 55 (GPR55), G-coupled protein receptor 119 (GPR119), and claudins-1, -2, -3, -4, -5, -7, and -8 mRNA were measured using multiplex. Aquaporin 3 and 4 were measured using enzyme-linked immunosorbent assay (ELISA). A randomized, double-blind, controlled-trial assessed the effect of PEA or CBD on the absorption of lactulose and mannitol in humans taking 600 mg of aspirin. Urinary concentrations of these sugars were measured using liquid chromatography mass spectrometry. Results In vitro, PEA, and CBD decreased the Inflammation-induced flux of dextrans (P < 0.0001), sensitive to PPARα and CB1 antagonism, respectively. Both PEA and CBD were prevented by PKA, MEK/ERK, and adenylyl cyclase inhibition (P < 0.001). In human Mucosa, Inflammation decreased claudin-5 mRNA, which was prevented by CBD (P < 0.05). Palmitoylethanolamide and cannabidiol prevented an Inflammation-induced fall in TRPV1 and increase in PPARα transcription (P < 0.0001). In vivo, aspirin caused an increase in the absorption of lactulose and mannitol, which were reduced by PEA or CBD (P < 0.001). Conclusion Cannabidiol and palmitoylethanolamide reduce permeability in the human colon. These findings have implications in disorders associated with increased gut permeability, such as inflammatory bowel disease.