Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State both In Vitro and In Vivo Models of Neuroinflammation

• Published in: Frontiers in neurology 2017-06, Vol.8, p.251-251
• Main Authors: Calvello, Rosa, Lofrumento, Dario Domenico, Perrone, Maria Grazia, Cianciulli, Antonia, Salvatore, Rosaria, Vitale, Paola, De Nuccio, Francesco, Giannotti, Laura, Nicolardi, Giuseppe, Panaro, Maria Antonietta, Scilimati, Antonio
• Format: Article
• Language: English
• Subjects: cyclooxygenase-1; cyclooxygenase-1 inhibitors; in vitro and in vivo experiments; lipopolysaccharide-treated BV2 microglial cells; neuroinflammation; Neuroscience; P6 and mofezolac
• ISSN: 1664-2295; 1664-2295
• DOI: 10.3389/fneur.2017.00251

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 and 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 PGE release reduction and NF-kB activation downregulation. Coextensively, in the 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 treatment with mofezolac as well as PGE 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.