4 results on '"Simona, Pace"'
Search Results
2. Differential role of vacuolar (H
- Author
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Zhigang, Rao, Paul M, Jordan, Yan, Wang, Dirk, Menche, Simona, Pace, Jana, Gerstmeier, and Oliver, Werz
- Subjects
Adult ,Lipopolysaccharides ,Leukotrienes ,Vacuolar Proton-Translocating ATPases ,Adolescent ,MAP Kinase Signaling System ,Gene Expression ,Hydrogen-Ion Concentration ,Middle Aged ,Healthy Volunteers ,Young Adult ,Cyclooxygenase 2 ,Leukocytes, Mononuclear ,Prostaglandins ,Humans ,Enzyme Inhibitors ,Cells, Cultured ,Aged - Abstract
Monocytes are professional immune cells that produce abundant levels of pro-inflammatory eicosanoids including prostaglandins and leukotrienes during inflammation. Vacuolar (H
- Published
- 2019
Catalog
3. Differential role of vacuolar (H+)-ATPase in the expression and activity of cyclooxygenase-2 in human monocytes
- Author
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Paul M. Jordan, Oliver Werz, Yan Wang, Zhigang Rao, Simona Pace, Jana Gerstmeier, and Dirk Menche
- Subjects
0301 basic medicine ,Pharmacology ,biology ,Kinase ,Chemistry ,p38 mitogen-activated protein kinases ,Intracellular pH ,Inflammation ,Lipid signaling ,Biochemistry ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Eicosanoid ,030220 oncology & carcinogenesis ,medicine ,biology.protein ,Phosphorylation ,Cyclooxygenase ,medicine.symptom - Abstract
Monocytes are professional immune cells that produce abundant levels of pro-inflammatory eicosanoids including prostaglandins and leukotrienes during inflammation. Vacuolar (H+)-ATPase (V-ATPase) is critically involved in a variety of inflammatory processes including cytokine trafficking and lipid mediator biosynthesis. However, its role in eicosanoid biosynthetic pathways in monocytes remains elusive. Here, we present a differential role of V-ATPase in the expression and in the activity of cyclooxygenase (COX)-2 in human monocytes. Pharmacological targeting of V-ATPase increased the expression of COX-2 protein in lipopolysaccharide-stimulated primary monocytes, which was paralleled by enhanced phosphorylation of p38 MAPK and ERK-1/2, without impacting the NF-κB and SAPK/JNK pathways. Targeting of both p38 MAPK and ERK-1/2 pathways showed that the kinase pathways are crucial for COX-2 expression in human monocytes. Despite increased COX-2 protein levels, however, suppression of V-ATPase activity impaired the biosynthesis of COX- and also of 5-lipoxygenase (LOX)-derived lipid mediators in monocytes without affecting 12-/15-LOX products, assessed by a metabololipidomics approach using UPLC-MS-MS analysis. Our results indicate that changes in the intracellular pH may contribute to suppression of COX-2 and 5-LOX activities. We suggest that V-ATPase on one hand limits COX-2 protein levels via restricting p38 MAPK and ERK-1/2 activation, while on the other hand it governs the cellular activity of COX-2 through appropriate adjustment of the intracellular pH. more...
- Published
- 2020
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4. The 5-lipoxygenase inhibitor RF-22c potently suppresses leukotriene biosynthesis in cellulo and blocks bronchoconstriction and inflammation in vivo
- Author
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Maria Scuotto, Fioretina Roviezzo, Mario De Rosa, Verena Krauth, Simona Pace, Daniela Schuster, Antonella Peduto, Ulrike Garscha, Rosanna Filosa, Hermann Stuppner, Selene Collarile, Giuseppe Spaziano, Christina Weinigel, Oliver Werz, Stefanie Liening, Anja M. Schaible, Bruno D'Agostino, Markus Nett, Sebastian Schieferdecker, Veronika Temml, Silke Rummler, Schaible, A. M., Filosa, R., Krauth, V., Temml, V., Pace, S., Garscha, U., Liening, S., Weinigel, C., Rummler, S., Schieferdecker, S., Nett, M., Peduto, A., Collarile, S., Scuotto, M., Roviezzo, F., Spaziano, G., De Rosa, M., Stuppner, H., Schuster, D., D'Agostino, B., Werz, O., Schaible, Anja M., Filosa, Rosanna, Krauth, Verena, Temml, Veronika, Pace, Simona, Garscha, Ulrike, Liening, Stefanie, Weinigel, Christina, Rummler, Silke, Schieferdecker, Sebastian, Nett, Marku, Peduto, Antonella, Collarile, Selene, Scuotto, Maria, Roviezzo, Fiorentina, Spaziano, Giuseppe, De Rosa, Mario, Stuppner, Hermann, Schuster, Daniela, D'Agostino, Bruno, Werz, Oliver, Roviezzo, Fioretina, and DE ROSA, Mario more...
- Subjects
0301 basic medicine ,Neutrophils ,Anti-Inflammatory Agents ,Pharmacology ,Monocyte ,Benzoquinone ,Biochemistry ,Monocytes ,chemistry.chemical_compound ,0302 clinical medicine ,Benzoquinones ,Edema ,Lipoxygenase Inhibitors ,Cells, Cultured ,5-Lipoxygenase ,Leukotriene ,Mice, Inbred BALB C ,biology ,Chemistry ,Neutrophil ,Molecular Docking Simulation ,Anti-Inflammatory Agent ,030220 oncology & carcinogenesis ,Arachidonate 5-lipoxygenase ,Bronchoconstriction ,Arachidonic acid ,Female ,medicine.symptom ,Human ,Blood Platelets ,Leukotrienes ,Inflammation ,Lipoxygenase Inhibitor ,03 medical and health sciences ,In vivo ,medicine ,Escherichia coli ,Animals ,Humans ,DAPI ,Arachidonate 5-Lipoxygenase ,Animal ,Leukocyte ,030104 developmental biology ,biology.protein ,Blood Platelet ,Cyclooxygenase - Abstract
5-Lipoxygenase (5-LO) catalyzes the first two steps in leukotriene (LT) biosynthesis. Because LTs play pivotal roles in allergy and inflammation, 5-LO represents a valuable target for anti-inflammatory drugs. Here, we investigated the molecular mechanism, the pharmacological profile, and the in vivo effectiveness of the novel 1,2-benzoquinone-featured 5-LO inhibitor RF-22c. Compound RF-22c potently inhibited 5-LO product synthesis in neutrophils and monocytes (IC50 ≥ 22 nM) and in cell-free assays (IC50 ≥ 140 nM) without affecting 12/15-LOs, cyclooxygenase (COX)-1/2, or arachidonic acid release, in a specific and reversible manner, supported by molecular docking data. Antioxidant or iron-chelating properties were not evident for RF-22c and 5-LO-regulatory cofactors like Ca2+ mobilization, ERK-1/2 activation, and 5-LO nuclear membrane translocation and interaction with 5-LO-activating protein (FLAP) were unaffected. RF-22c (0.1 mg/kg; i.p.) impaired (I) bronchoconstriction in ovalbumin-sensitized mice challenged with acetylcholine, (II) exudate formation in carrageenan-induced paw edema, and (III) zymosan-induced leukocyte infiltration in air pouches. Taken together, RF-22c is a highly selective and potent 5-LO inhibitor in intact human leukocytes with pronounced effectiveness in different models of inflammation that warrants further preclinical analysis of this agent as anti-inflammatory drug. more...
- Published
- 2016
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