21 results on '"Iuvone T"'
Search Results
2. ChemInform Abstract: A New Antiproliferative Sulfated Alkene from the Mediterranean Tunicate Microcosmus vulgaris.
- Author
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AIELLO, A., primary, FATTORUSSO, E., additional, MENNA, M., additional, CARNUCCIO, R., additional, and IUVONE, T., additional
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- 2010
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3. Protective role of palmitoylethanolamide in contact allergic dermatitis
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Petrosino, S., primary, Cristino, L., additional, Karsak, M., additional, Gaffal, E., additional, Ueda, N., additional, Tüting, T., additional, Bisogno, T., additional, De Filippis, D., additional, D’Amico, A., additional, Saturnino, C., additional, Orlando, P., additional, Zimmer, A., additional, Iuvone, T., additional, and Di Marzo, V., additional
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- 2009
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4. Increased mucosal nitric oxide production in ulcerative colitis is mediated in part by the enteroglial-derived S100B protein
- Author
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cirillo, c., primary, sarnelli, g., additional, esposito, g., additional, grosso, m., additional, petruzzelli, r., additional, izzo, p., additional, calì, g., additional, d’armiento, f. p., additional, rocco, a., additional, nardone, g., additional, iuvone, t., additional, steardo, l., additional, and cuomo, r., additional
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- 2009
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5. Cannabinoids reduce granuloma-associated angiogenesis in rats by controlling transcription and expression of mast cell protease-5
- Author
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De Filippis, D, primary, Russo, A, additional, D'Amico, A, additional, Esposito, G, additional, Concetta, P, additional, Cinelli, M, additional, Russo, G, additional, and Iuvone, T, additional
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- 2008
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6. Effect of cannabidiol on sepsis-induced motility disturbances in mice: involvement of CB1receptors and fatty acid amide hydrolase
- Author
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de filippis, d., primary, iuvone, t., additional, d'amico, a., additional, esposito, g., additional, steardo, l., additional, herman, a. g., additional, pelckmans, p. a., additional, de winter, b. y., additional, and de man, j. g., additional
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- 2008
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7. Cannabinomimetic Control of Mast Cell Mediator Release: New Perspective in Chronic Inflammation
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De Filippis, D., primary, D’Amico, A., additional, and Iuvone, T., additional
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- 2008
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8. Cannabidiol in vivo blunts β‐amyloid induced neuroinflammation by suppressing IL‐1β and iNOS expression
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Esposito, G, primary, Scuderi, C, additional, Savani, C, additional, Steardo, L, additional, De Filippis, D, additional, Cottone, P, additional, Iuvone, T, additional, and Cuomo, V, additional
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- 2007
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9. Involvement of NF-κB in the regulation of cyclooxygenase-2 protein expression in LPS-stimulated J774 macrophages
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Rosa Carnuccio, Fulvio D'Acquisto, Laura Rombolà, Teresa Iuvone, Lidia Sautebin, Massimo Di Rosa, D'Acquisto, F., Iuvone, T., Rombola', L., Sautebin, Lidia, DI ROSA, M., Carnuccio, Rosa, D'Acquisto, F, Iuvone, T, Rombola', L, Sautebin, L, and DI ROSA, Massimo
- Subjects
Lipopolysaccharides ,Proline ,Prostaglandin ,Biophysics ,Inflammation ,6-Ketoprostaglandin F1 alpha ,Biology ,Tosyllysine Chloromethyl Ketone ,Biochemistry ,Dinoprostone ,Gene Expression Regulation, Enzymologic ,NF-κB ,Cell Line ,chemistry.chemical_compound ,Cytosol ,Structural Biology ,Genetics ,medicine ,Animals ,Tosyl-lysine chloromethylketone ,Molecular Biology ,Incubation ,Cell Nucleus ,Regulation of gene expression ,Macrophages ,NF-kappa B ,Prostanoid ,Cell Biology ,COX-2 ,Molecular biology ,Ammonium pyrrolidinedithiocarbamate ,Isoenzymes ,Kinetics ,chemistry ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Cell culture ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Cyclooxygenase ,medicine.symptom - Abstract
We investigated the involvement of NF-kappaB in the regulation of COX-2 protein expression and prostaglandin production in LPS-stimulated J774 macrophages. Incubation of J774 cells with LPS (1 microg/ml) for 24 h caused an increase of COX-2 protein expression and accumulation of both PGE2 and 6-keto-PGF1alpha in the cell culture medium. Ammonium pyrrolidinedithiocarbamate (APDC, 0.1, 1, 10 microM) and N-alpha-p-tosyl-L-lysine chloromethylketone (TLCK, 1, 10, 100 microM), two inhibitors of NF-kappaB activation, suppressed in a concentration-dependent manner both LPS-induced COX-2 protein expression and prostanoid generation. Moreover, APDC and TLCK both inhibited the LPS-induced increase of NF-kappaB DNA binding activity and prevented IkappaB-alpha degradation. Our results show for the first time that NF-kappaB is involved in COX-2 protein expression in LPS-stimulated J774 macrophages and suggest that inhibitors of NF-kappaB activation may represent a useful tool for the pharmacological control of inflammation.
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- 1997
10. Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF Signaling in Caco-2 Human Colon Carcinoma Cell Line Through a Selective PPAR-α-Dependent Inhibition of Akt/mTOR Pathway.
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Sarnelli G, Gigli S, Capoccia E, Iuvone T, Cirillo C, Seguella L, Nobile N, D'Alessandro A, Pesce M, Steardo L, Cuomo R, and Esposito G
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- Amides, Animals, Caco-2 Cells, Cell Line, Tumor, Cell Proliferation, Down-Regulation drug effects, Ethanolamines therapeutic use, Humans, Neovascularization, Pathologic, Palmitic Acids therapeutic use, Signal Transduction, Colonic Neoplasms drug therapy, Ethanolamines chemistry, PPAR alpha metabolism, Palmitic Acids chemistry, Vascular Endothelial Growth Factor A metabolism
- Abstract
Palmitoylethanolamide (PEA) is a nutraceutical compound that has been demonstrated to improve intestinal inflammation. We aimed at evaluating its antiproliferative and antiangiogenic effects in human colon adenocarcinoma Caco-2 cell line. Caco-2 cells were treated with increasing concentrations of PEA (0.001, 0.01 and 0.1 μM) in the presence of peroxisome proliferator-activated receptor-a (PPAR-α) or PPAR-γ antagonists. Cell proliferation was evaluated by performing a MTT assay. Vascular endothelial growth factor (VEGF) release was estimated by ELISA, while the expression of VEGF receptor and the activation of the Akt/mammalian target of rapamycin (mTOR) pathway were evaluated by western blot analysis. PEA caused a significant and concentration-dependent decrease of Caco-2 cell proliferation at 48 h. PEA administration significantly reduced in a concentration-dependent manner VEGF secretion and VEGF receptor expression. Inhibition of Akt phosphorylation and a downstream decrease of phospho-mTOR and of p-p70S6K were observed as compared with untreated cells. PPAR-α, but not PPAR-γ antagonist, reverted all effects of PEA. PEA is able to decrease cell proliferation and angiogenesis. The antiangiogenic effect of PEA depends on the specific inhibition of the AkT/mTOR axis, through the activation of PPAR-α pathway. If supported by in vivo models, our data pave the way to PEA co-administration to the current chemotherapeutic regimens for colon carcinoma. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)
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- 2016
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11. Cannabidiol in inflammatory bowel diseases: a brief overview.
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Esposito G, Filippis DD, Cirillo C, Iuvone T, Capoccia E, Scuderi C, Steardo A, Cuomo R, and Steardo L
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- Humans, Inflammation drug therapy, Phytotherapy, Plant Extracts therapeutic use, Cannabidiol therapeutic use, Gastrointestinal Agents therapeutic use, Inflammatory Bowel Diseases drug therapy
- Abstract
This minireview highlights the importance of cannabidiol (CBD) as a promising drug for the therapy of inflammatory bowel diseases (IBD). Actual pharmacological treatments for IBD should be enlarged toward the search for low-toxicityand low-cost drugs that may be given alone or in combination with the conventional anti-IBD drugs to increase their efficacy in the therapy of relapsing forms of colitis. In the past, Cannabis preparations have been considered new promising pharmacological tools in view of their anti-inflammatory role in IBD as well as other gut disturbances. However, their use in the clinical therapy has been strongly limited by their psychotropic effects. CBD is a very promising compound since it shares the typical cannabinoid beneficial effects on gut lacking any psychotropic effects. For years, its activity has been enigmatic for gastroenterologists and pharmacologists, but now it is evident that this compound may interact at extra-cannabinoid system receptor sites, such as peroxisome proliferator-activated receptor-gamma. This strategic interaction makes CBD as a potential candidate for the development of a new class of anti-IBD drugs., (Copyright © 2012 John Wiley & Sons, Ltd.)
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- 2013
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12. Cannabidiol in medicine: a review of its therapeutic potential in CNS disorders.
- Author
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Scuderi C, Filippis DD, Iuvone T, Blasio A, Steardo A, and Esposito G
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- Animals, Cannabidiol therapeutic use, Cannabidiol toxicity, Humans, Cannabidiol pharmacology, Cannabis chemistry, Central Nervous System Diseases drug therapy
- Abstract
Cannabidiol (CBD) is the main non-psychotropic component of the glandular hairs of Cannabis sativa. It displays a plethora of actions including anticonvulsive, sedative, hypnotic, antipsychotic, antiinflammatory and neuroprotective properties. However, it is well established that CBD produces its biological effects without exerting significant intrinsic activity upon cannabinoid receptors. For this reason, CBD lacks the unwanted psychotropic effects characteristic of marijuana derivatives, so representing one of the bioactive constituents of Cannabis sativa with the highest potential for therapeutic use.The present review reports the pharmacological profile of CBD and summarizes results from preclinical and clinical studies utilizing CBD, alone or in combination with other phytocannabinoids, for the treatment of a number of CNS disorders.
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- 2009
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13. Melatonin reverses lipopolysaccharide-induced gastro-intestinal motility disturbances through the inhibition of oxidative stress.
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De Filippis D, Iuvone T, Esposito G, Steardo L, Arnold GH, Paul AP, De Man Joris G, and De Winter Benedicte Y
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- Animals, Antioxidants therapeutic use, Gastroenteritis chemically induced, Lipopolysaccharides toxicity, Male, Melatonin therapeutic use, Mice, Antioxidants pharmacology, Gastroenteritis drug therapy, Gastrointestinal Motility drug effects, Melatonin pharmacology, Oxidative Stress drug effects
- Abstract
A growing number of reports demonstrate that a pro-inflammatory and oxidative condition is related to the pathogenesis and the progression of endotoxin-induced septic shock and that antioxidants may have therapeutic potential in lipopolysaccharide (LPS)-induced sepsis. Melatonin has been shown to possess potent antioxidant properties in several models of inflammation in mice and rats. In the present study we focused on the possible protective mechanism of melatonin in preventing gastrointestinal (GI) disturbances induced by LPS in mice. In fact, mice treated with LPS showed a reduced gastric emptying of solid beads. Also the geometric center, representing the relative distribution of the solid beads throughout the entire GI tract, was significantly reduced in LPS-treated mice confirming that sepsis leads to a disturbed GI motility in mice. Melatonin completely reversed the LPS-induced motility disturbance. This beneficial effect of melatonin is associated with a reduction in lipid peroxidation, MAPK activation, NF-kappaB activation, iNOS transcription and expression and nitrite production in intestinal tissue from septic mice. These results demonstrate that melatonin prevents the LPS-induced GI disturbances in mice switching off the pro-oxidant pathways induced by the endotoxin. Therefore, it is reasonable to propose melatonin as a molecule with therapeutic potential for the treatment of systemic inflammation by interfering at the earliest steps of activation of the oxidative and pro-inflammatory cascade.
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- 2008
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14. Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression.
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Esposito G, Scuderi C, Savani C, Steardo L Jr, De Filippis D, Cottone P, Iuvone T, Cuomo V, and Steardo L
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- Animals, Cannabidiol administration & dosage, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Gene Expression Regulation, Glial Fibrillary Acidic Protein metabolism, Hippocampus, Inflammation chemically induced, Interleukin-1beta drug effects, Interleukin-1beta metabolism, Mice, Mice, Inbred C57BL, Neuroprotective Agents administration & dosage, Nitric Oxide metabolism, Nitric Oxide Synthase Type II drug effects, Nitric Oxide Synthase Type II metabolism, RNA, Messenger, Amyloid beta-Peptides toxicity, Cannabidiol pharmacology, Inflammation drug therapy, Neuroprotective Agents pharmacology, Neurotoxicity Syndromes drug therapy, Peptide Fragments toxicity
- Abstract
Background and Purpose: Pharmacological inhibition of beta-amyloid (Abeta) induced reactive gliosis may represent a novel rationale to develop drugs able to blunt neuronal damage and slow the course of Alzheimer's disease (AD). Cannabidiol (CBD), the main non-psychotropic natural cannabinoid, exerts in vitro a combination of neuroprotective effects in different models of Abeta neurotoxicity. The present study, performed in a mouse model of AD-related neuroinflammation, was aimed at confirming in vivo the previously reported antiinflammatory properties of CBD., Experimental Approach: Mice were inoculated with human Abeta (1-42) peptide into the right dorsal hippocampus, and treated daily with vehicle or CBD (2.5 or 10 mg kg(-1), i.p.) for 7 days. mRNA for glial fibrillary acidic protein (GFAP) was assessed by in situ hybridization. Protein expression of GFAP, inducible nitric oxide synthase (iNOS) and IL-1beta was determined by immunofluorescence analysis. In addition, ELISA assay of IL-1beta level and the measurement of NO were performed in dissected and homogenized ipsilateral hippocampi, derived from vehicle and Abeta inoculated mice, in the absence or presence of CBD., Key Results: In contrast to vehicle, CBD dose-dependently and significantly inhibited GFAP mRNA and protein expression in Abeta injected animals. Moreover, under the same experimental conditions, CBD impaired iNOS and IL-1beta protein expression, and the related NO and IL-1beta release., Conclusion and Implications: The results of the present study confirm in vivo anti-inflammatory actions of CBD, emphasizing the importance of this compound as a novel promising pharmacological tool capable of attenuating Abeta evoked neuroinflammatory responses.
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- 2007
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15. Inhibition of granuloma-associated angiogenesis by controlling mast cell mediator release: role of mast cell protease-5.
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Russo A, Russo G, Peticca M, Pietropaolo C, Di Rosa M, and Iuvone T
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- Animals, Cell Degranulation drug effects, Cell Degranulation physiology, Gene Expression drug effects, Male, Mast Cells metabolism, Rats, Rats, Wistar, Granuloma physiopathology, Ketotifen pharmacology, Mast Cells drug effects, Neovascularization, Pathologic physiopathology, Serine Endopeptidases metabolism
- Abstract
We investigated the role of mast cells in granuloma-associated angiogenesis in rat by using: (i) a mast cell membrane stabilizer, ketotifen; (ii) a mast cell depleting agent, compound 48/80. Moreover, we focused on the role of chymases, which exhibit proinflammatory and pro-angiogenic properties by using: (i) chymostatin, an inhibitor of chymase activity; (ii) a specific antisense oligonucleotide (AS-ODN) designed against rat mast cell protease-5 (rMCP-5), the most abundantly expressed chymase in the skin. The formation of granuloma was evaluated, as wet weight, 96 h after the subcutaneous implant of two lambda-carrageenin (1%)-soaked sponges on the back of male Wistar rats. Angiogenesis was evaluated as haemoglobin content in the granulomatous tissue and as level of tumour necrosis factor-alpha (TNF-alpha) in the exudates. A single injection of ketotifen (1-5-25 mg kg(-1) i.p.) significantly reduced granuloma formation by 31.6, 44.6 and 71.9%, and haemoglobin content by 17.0, 35.0 and 66.2%, suggesting that the release of mediator(s) from mast cells modulates the process. Chymostatin (5-10 nmol(-1) site(-1) day(-1)) reduced granuloma-associated angiogenesis by 57.3 and 70.0%. RT-PCR analysis showed that rMCP-5 mRNA amounts were significantly reduced by rMCP-5 AS-ODN (1.25-2.5-5.0 nmol site(-1)) by 69.5, 72.5 and 81.8%. In parallel experiments, rMCP-5 AS-ODN (1.25, 2.5, 5.0 nmol site(-1)) strongly reduced granuloma weight (26.1, 45.0 and 56.3%) and haemoglobin content (22.2, 50.4, 62.03%), suggesting that the observed effect is mediated through an antisense mechanism. In conclusion, these data suggest that: (i) inhibition of mast cell mediators release may represent a novel strategy to modulate angiogenesis; (ii) among the chymase family, rMCP-5 is a key promoter of angiogenesis in the rat.
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- 2005
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16. Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation.
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Izzo AA, Fezza F, Capasso R, Bisogno T, Pinto L, Iuvone T, Esposito G, Mascolo N, Di Marzo V, and Capasso F
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- Analgesics pharmacology, Analgesics therapeutic use, Animals, Cannabinoid Receptor Modulators, Cannabinoids agonists, Cannabinol pharmacology, Cannabinol therapeutic use, Croton Oil, Cyclohexanols pharmacology, Cyclohexanols therapeutic use, Dermatologic Agents, Dose-Response Relationship, Drug, Gastrointestinal Motility drug effects, Inflammatory Bowel Diseases chemically induced, Inflammatory Bowel Diseases drug therapy, Inflammatory Bowel Diseases metabolism, Injections, Intraperitoneal, Injections, Intraventricular, Male, Mice, Mice, Inbred ICR, Piperidines pharmacology, Pyrazoles pharmacology, Receptors, Cannabinoid, Receptors, Drug antagonists & inhibitors, Receptors, Drug biosynthesis, Rimonabant, Cannabinoids metabolism, Disease Models, Animal, Gastrointestinal Motility physiology, Inflammatory Bowel Diseases physiopathology, Receptors, Drug physiology
- Abstract
1. We have studied the effect of cannabinoid agonists (CP 55,940 and cannabinol) on intestinal motility in a model of intestinal inflammation (induced by oral croton oil in mice) and measured cannabinoid receptor expression, endocannabinoids (anandamide and 2-arachidonylglycerol) and anandamide amidohydrolase activity both in physiological and pathophysiological states. 2. CP 55,940 (0.03 - 10 nmol mouse(-1)) and cannabinol (10 - 3000 nmol mouse(-1)) were more active in delaying intestinal motility in croton oil-treated mice than in control mice. These inhibitory effects were counteracted by the selective cannabinoid CB(1) receptor antagonist SR141716A (16 nmol mouse(-1)). SR141716A (1 - 300 nmol mouse(-1)), administered alone, increased intestinal motility to the same extent in both control and croton oil-treated mice. 3. Croton oil-induced intestinal inflammation was associated with an increased expression of CB(1) receptor, an unprecedented example of up-regulation of cannabinoid receptors during inflammation. 4. High levels of anandamide and 2-arachidonylglycerol were detected in the small intestine, although no differences were observed between control and croton oil-treated mice; by contrast anandamide amidohydrolase activity increased 2 fold in the inflamed small intestine. 5. It is concluded that inflammation of the gut increases the potency of cannabinoid agonists possibly by 'up-regulating' CB(1) receptor expression; in addition, endocannabinoids, whose turnover is increased in inflamed gut, might tonically inhibit intestinal motility.
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- 2001
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17. Evidence that mast cell degranulation, histamine and tumour necrosis factor alpha release occur in LPS-induced plasma leakage in rat skin.
- Author
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Iuvone T, Den Bossche RV, D'Acquisto F, Carnuccio R, and Herman AG
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- Animals, Antibodies pharmacology, Ketotifen pharmacology, Male, Mast Cells metabolism, Rats, Rats, Wistar, Skin blood supply, Skin cytology, Tumor Necrosis Factor-alpha immunology, Capillary Permeability drug effects, Cell Degranulation, Histamine Release, Lipopolysaccharides pharmacology, Mast Cells drug effects, Skin drug effects, Tumor Necrosis Factor-alpha metabolism
- Abstract
1. In the present study we investigated the role of mast cells during inflammation in rat skin. As the release of several pro-inflammatory mediators, such as histamine and tumour necrosis factor alpha (TNFalpha), occurs following mast cell activation we studied whether mast cell degranulation and the release of both histamine (H) and TNFalpha occurred in a model of lipopolysaccharide (LPS)-induced plasma leakage in rat skin. 2. Plasma leakage in the rat skin was measured over a period of 2 h as the local accumulation of intravenous injection of 125I-human serum albumin (125I-HSA) in response to intradermal injection of LPS. LPS (10 microg site-1) produced an increase of plasma leakage (50.1+/-2.3 microl site-1) as compared to saline (9.0+/-3.2 microl site-1). Histological analysis of rat tissue showed that LPS induced a remarkable mast cell degranulation (59.8+/-2.1%) as compared to saline (13.5+/-2.2%). 3. Ketotifen (10-9 - 10-7 mol site-1), a well-known mast cell-membrane stabilizer, produced a dose-related inhibition of LPS-induced plasma leakage by 36+/-3.5%, 47+/-4.0%, 60+/-3.3% respectively. In addition, ketotifen (10-7 mol site-1) inhibited mast cell degranulation by 59. 2+/-2.7%. 4. Chlorpheniramine maleate (CPM) (10-9 - 10-7 mol site-1), an H1 histamine receptor antagonist only partially inhibited LPS-induced plasma leakage in rat skin (38+/-1.1% at the highest dose). Furthermore, CPM (10-7 mol site-1) did not prevent mast cell degranulation. 5. A polyclonal antibody against TNFalpha (1:500, 1:100, 1:50 v v-1 dilution), locally injected, decreased LPS-induced plasma leakage in the skin by 15+/-2.0%, 24+/-2.1% and 50+/-3.0% respectively. 6. Taken together these results suggest that LPS-induced plasma leakage in rat skin is mediated, at least in part, by mast cell degranulation and by the release of histamine and TNFalpha from these cells.
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- 1999
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18. Evidence that inducible nitric oxide synthase is involved in LPS-induced plasma leakage in rat skin through the activation of nuclear factor-kappaB.
- Author
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Iuvone T, D'Acquisto F, Van Osselaer N, Di Rosa M, Carnuccio R, and Herman AG
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- Animals, Enzyme Induction, Enzyme Inhibitors pharmacology, Male, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide physiology, Nitric Oxide Synthase antagonists & inhibitors, Nitric Oxide Synthase biosynthesis, Nitric Oxide Synthase Type II, Pyrrolidines pharmacology, Rats, Rats, Wistar, Skin blood supply, Thiocarbamates pharmacology, Capillary Permeability drug effects, Lipopolysaccharides pharmacology, NF-kappa B metabolism, Nitric Oxide Synthase metabolism, Skin drug effects
- Abstract
1. Rats challenged with lipopolysaccharide (LPS) produce large amounts of nitric oxide (NO) following the induction of the inducible NO-synthase (iNOS) in several tissues and organs. Recent studies have shown that the expression of iNOS is regulated at the transcriptional level by a transcription nuclear factor-kappaB (NF-kappaB). In this study we investigated the role of NO in a model of LPS-induced plasma-leakage in rat skin and the involvement of NF-kappaB. 2. Plasma leakage in the rat skin was measured over a period of 30 min to 2 h as the local accumulation of intravenous (i.v.) injection of [125I]-human serum albumin ([125I]-HSA) in response to intradermal (i.d.) injection of LPS. LPS (1, 10, 100 microg/site) produced a dose-related increase in plasma extravasation (18.2+/-3.2, 27.2+/-2.9, 40.4+/-9.6 microl/site) as compared to saline control (11.4+/-2.2 microl/site). This increase was maximal after 2 h; therefore this time point and the dose of LPS 10 microg/site was used in all the successive experiments. 3. To investigate the role of NO in LPS-induced plasma leakage in rat skin, the non-selective NOS inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the more selective iNOS inhibitor S-methyl-isothiourea (SMT) was injected i.d. with LPS. L-NAME and SMT (0.01, 0.1 and 1 micromol/site) inhibited LPS-induced plasma leakage in a dose-related fashion (L-NAME: 26.0+/-5.5, 20.2+/-1.6, 18.0+/-2.0 microl/site; SMT: 19.5+/-1.5, 17.0+/-1.6, 15.0+/-2.6 microl/site) as compared to LPS alone (27.2+/-2.9 microl/site). At the lowest concentration used (0.01 micromol/site), SMT significantly reduced plasma leakage by 30%+/-0.7 while L-NAME (0.01 micromol/site) was not effective. 4. Treatment with increasing concentrations of pyrrolidinedithyocarbamate (PDTC) (0.01, 0.1, 1 micromol/site), an inhibitor of NF-kappaB activation, injected i.d. 30 min before LPS challenge, inhibited in a concentration-dependent fashion LPS-induced plasma leakage by 9.0+/-0.6, 33+/-4.0, 51+/-2.0% respectively. Moreover, PDTC (0.1, 1 micromol/site) suppressed LPS-induced NF-kappaB DNA-binding. 5. Western blot analysis showed significant levels of iNOS proteins in the skin samples of LPS-treated rats, as compared to basal levels present in saline-injected rat skin. PDTC (0.1, 1.0 micromol/site) dose-dependently decreased the amount of iNOS protein expression induced by LPS. 6. Our results indicate that LPS-induced plasma leakage in rat skin is modulated by NO mainly produced by the inducible isoform of NOS. Furthermore, the suppression of plasma leakage by PDTC, an inhibitor of NF-kappaB activation, is correlated to the inhibition of iNOS protein expression.
- Published
- 1998
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19. Differential effect of L-NAME and S-methyl-isothiourea on leukocyte emigration in carrageenin-soaked sponge implants in rat.
- Author
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Iuvone T, Van Osselaer N, D'Acquisto F, Carnuccio R, and Herman AG
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- Animals, Arginine pharmacology, Capillary Permeability drug effects, Carrageenan, Cell Movement drug effects, Epoprostenol biosynthesis, Isothiuronium pharmacology, Leukocytes physiology, Male, Nitrites metabolism, Rats, Rats, Wistar, Tumor Necrosis Factor-alpha biosynthesis, Enzyme Inhibitors pharmacology, Inflammation blood, Isothiuronium analogs & derivatives, Leukocytes drug effects, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide physiology, Nitric Oxide Synthase antagonists & inhibitors
- Abstract
1. The role of nitric oxide (NO) in leukocyte (polymorphonuclear cells, monocytes and lymphocytes) emigration was studied in a model of carrageenin-sponge implants in rats. 2. The subcutaneous implantation of 1% (w/v) of lambda-carrageenin-soaked sponges elicited an inflammatory response that was characterized by a time-related increase in leukocyte infiltration in the sponges and increased levels of nitrite in the exudate. Total leukocyte infiltration and nitrite production were maximal at 24 h and decreased after 48 and 96 h. The mononuclear cell influx was maximal at 48 h (21% of the total leukocytes). Therefore, this time point was used in the successive experiments. 3. Polymorphonuclear cell (PMN) and lymphocyte infiltration in the sponges significantly increased when rats were treated with the non-specific NO-synthase (NOS) inhibitor, NG-nitro-L-arginine methylester (L-NAME) (1 mg ml-1) in drinking water ad libitum). Monocyte emigration was not affected by L-NAME treatment. The nitrite levels in the exudate of L-NAME-treated rats were significantly reduced. The concomitant ingestion of L-arginine (30 mg ml-1) resulted in a reversion of the L-NAME effect, while D-arginine (30 mg ml-1) had no effect, indicating the involvement of the L-arginine: NO pathway. 4. Administration of L-NAME resulted also in an increased release of tumour necrosis factor-alpha (TNF-alpha) and prostacyclin (measured as the stable metabolite, 6-keto-PGF 1 alpha). L-NAME had no effect on monocyte chemoattractant protein-1 (MCP-1) release in the exudate. 5. Since L-NAME may have effects on the local blood flow, phenylephrine (0.034 mg ml-2) in drinking water) was used as it has an effect on the local blood flow similar to L-NAME. Phenylephrine had no effect on either leukocyte emigration, or on nitrite, TNF-alpha, prostacyclin or MCP-1 accumulation in the exudate. 6. In contrast, the more selective iNOS inhibitor S-methyl-isothiourea (SMT) (10 micrograms ml-1) in drinking water) significantly reduced PMNs and lymphocyte influx in the sponge having no effect on monocyte influx. Moreover, SMT decreased nitrite production in the exudate to a comparable extent as L-NAME. 7. Administration of SMT significantly reduced MCP-1 release in the exudate, without an effect on TNF-alpha or prostacyclin production. Moreover SMT did not produce any changes in local blood flow. 8. Our results show that a different outcome of the inflammatory process can be obtained depending on the types of NOS inhibitor used.
- Published
- 1997
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20. Vasocortin: a novel glucocorticoid-induced anti-inflammatory protein.
- Author
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Carnuccio R, Di Rosa M, Guerrasio B, Iuvone T, and Sautebin L
- Subjects
- Animals, Annexins, Glycoproteins biosynthesis, Glycoproteins physiology, Inflammation prevention & control, Male, Peritoneum metabolism, Rats, Rats, Inbred Strains, Glucocorticoids pharmacology, Inflammation physiopathology, Proteins physiology
- Abstract
The preliminary characterization of ;vasocortin' a novel glucocorticoid-induced anti-inflammatory protein, is described. Vasocortin is released into the rat peritoneal cavity following systemic dexamethasone administration, has an apparent mol. wt. of 100 kD and inhibits rat dextran oedema. Vasocortin is distinct from lipocortin and is likely to be associated with the anti-inflammatory effect of glucocorticoids.
- Published
- 1987
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21. Selective inhibition by vasocortin of histamine release induced by dextran and concanavalin-A from rat peritoneal cells.
- Author
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Carnuccio R, Di Rosa M, Ialenti A, Iuvone T, and Sautebin L
- Subjects
- Animals, Annexins, Calcimycin pharmacology, Male, Mast Cells drug effects, Peritoneal Cavity cytology, Rats, Steroids, p-Methoxy-N-methylphenethylamine pharmacology, Anti-Inflammatory Agents pharmacology, Concanavalin A pharmacology, Dextrans pharmacology, Histamine Release drug effects, Mast Cells metabolism, Proteins pharmacology
- Abstract
Vasocortin, a glucocorticoid-induced anti-inflammatory protein, has been purified from the peritoneal lavage fluid of dexamethasone-treated rats. Vasocortin inhibited the release of histamine from rat peritoneal cells stimulated by dextran or concanavalin A but did not alter the release induced by calcium ionophore A23187 or compound 48/80. This selective effect exhibited by vasocortin mimics the glucocorticoid inhibition of histamine release from rat mast cells.
- Published
- 1989
- Full Text
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