Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State both In Vitro and In Vivo Models of Neuroinflammation
Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are the pharmacological targets of...
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doaj-2483fbf0684b48f1b07c7a4fed5971de2020-11-24T21:36:02ZengFrontiers Media S.A.Frontiers in Neurology1664-22952017-06-01810.3389/fneur.2017.00251254736Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State both In Vitro and In Vivo Models of NeuroinflammationRosa Calvello0Dario Domenico Lofrumento1Maria Grazia Perrone2Antonia Cianciulli3Rosaria Salvatore4Paola Vitale5Francesco De Nuccio6Laura Giannotti7Giuseppe Nicolardi8Maria Antonietta Panaro9Antonio Scilimati10Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari “A. Moro”, Bari, ItalyDepartment of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, ItalyDepartment of Pharmacy – Pharmaceutical Sciences, University of Bari “A. Moro”, Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari “A. Moro”, Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari “A. Moro”, Bari, ItalyDepartment of Pharmacy – Pharmaceutical Sciences, University of Bari “A. Moro”, Bari, ItalyDepartment of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, ItalyDepartment of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, ItalyDepartment of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari “A. Moro”, Bari, ItalyDepartment of Pharmacy – Pharmaceutical Sciences, University of Bari “A. Moro”, Bari, ItalyActivated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. Since it was reported that COX-1 is the major player in mediating the brain inflammatory response, the aim of this study was to evaluate the effects of highly selective COX-1 inhibitors, such as P6 and mofezolac, in neuroinflammation models. Lipopolysaccharide (LPS)-activated mouse BV-2 microglial cells and LPS intracerebroventricular-injected mice as in vitro and in vivo neuroinflammation models, respectively, were used to probe the antiinflammatory efficacy of P6 and mofezolac. Both P6 and mofezolac reduce COX-1 expression in LPS-activated BV-2 cells. This reduction was accompanied with PGE2 release reduction and NF-kB activation downregulation. Coextensively, in the in vivo model, both glial fibrillary acidic protein and ionized calcium-binding adapter molecule-1 expression, two markers of inflammation, were reduced by mofezolac to a rank depending on the encephalon area analyzed. The increase of COX-1 expression observed in all the brain sections of LPS-treated mice was selectively downregulated by the in vivo treatment with mofezolac as well as PGE2 release and Ikβα phosphorylation amount assayed in the brain areas tested. These results indicate the capability of P6 and mofezolac to modulate the NF-kB signaling pathway, emphasizing the neuroprotective effect and therapeutic potential of COX-1 inhibitors in the control of neuroinflammatory diseases.http://journal.frontiersin.org/article/10.3389/fneur.2017.00251/fullcyclooxygenase-1P6 and mofezolaccyclooxygenase-1 inhibitorsneuroinflammationin vitro and in vivo experimentslipopolysaccharide-treated BV2 microglial cells |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rosa Calvello Dario Domenico Lofrumento Maria Grazia Perrone Antonia Cianciulli Rosaria Salvatore Paola Vitale Francesco De Nuccio Laura Giannotti Giuseppe Nicolardi Maria Antonietta Panaro Antonio Scilimati |
spellingShingle |
Rosa Calvello Dario Domenico Lofrumento Maria Grazia Perrone Antonia Cianciulli Rosaria Salvatore Paola Vitale Francesco De Nuccio Laura Giannotti Giuseppe Nicolardi Maria Antonietta Panaro Antonio Scilimati Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State both In Vitro and In Vivo Models of Neuroinflammation Frontiers in Neurology cyclooxygenase-1 P6 and mofezolac cyclooxygenase-1 inhibitors neuroinflammation in vitro and in vivo experiments lipopolysaccharide-treated BV2 microglial cells |
author_facet |
Rosa Calvello Dario Domenico Lofrumento Maria Grazia Perrone Antonia Cianciulli Rosaria Salvatore Paola Vitale Francesco De Nuccio Laura Giannotti Giuseppe Nicolardi Maria Antonietta Panaro Antonio Scilimati |
author_sort |
Rosa Calvello |
title |
Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State both In Vitro and In Vivo Models of Neuroinflammation |
title_short |
Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State both In Vitro and In Vivo Models of Neuroinflammation |
title_full |
Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State both In Vitro and In Vivo Models of Neuroinflammation |
title_fullStr |
Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State both In Vitro and In Vivo Models of Neuroinflammation |
title_full_unstemmed |
Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State both In Vitro and In Vivo Models of Neuroinflammation |
title_sort |
highly selective cyclooxygenase-1 inhibitors p6 and mofezolac counteract inflammatory state both in vitro and in vivo models of neuroinflammation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2017-06-01 |
description |
Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. Since it was reported that COX-1 is the major player in mediating the brain inflammatory response, the aim of this study was to evaluate the effects of highly selective COX-1 inhibitors, such as P6 and mofezolac, in neuroinflammation models. Lipopolysaccharide (LPS)-activated mouse BV-2 microglial cells and LPS intracerebroventricular-injected mice as in vitro and in vivo neuroinflammation models, respectively, were used to probe the antiinflammatory efficacy of P6 and mofezolac. Both P6 and mofezolac reduce COX-1 expression in LPS-activated BV-2 cells. This reduction was accompanied with PGE2 release reduction and NF-kB activation downregulation. Coextensively, in the in vivo model, both glial fibrillary acidic protein and ionized calcium-binding adapter molecule-1 expression, two markers of inflammation, were reduced by mofezolac to a rank depending on the encephalon area analyzed. The increase of COX-1 expression observed in all the brain sections of LPS-treated mice was selectively downregulated by the in vivo treatment with mofezolac as well as PGE2 release and Ikβα phosphorylation amount assayed in the brain areas tested. These results indicate the capability of P6 and mofezolac to modulate the NF-kB signaling pathway, emphasizing the neuroprotective effect and therapeutic potential of COX-1 inhibitors in the control of neuroinflammatory diseases. |
topic |
cyclooxygenase-1 P6 and mofezolac cyclooxygenase-1 inhibitors neuroinflammation in vitro and in vivo experiments lipopolysaccharide-treated BV2 microglial cells |
url |
http://journal.frontiersin.org/article/10.3389/fneur.2017.00251/full |
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