Abstract

COX-1 plays a previously unrecognized part in the neuroinflammation. Genetic ablation or pharmacological inhibition of COX-1 activity attenuates the inflammatory response and neuronal loss. In this context, the effects of selective COX-1 inhibitors (P6, P10, SC-560, aspirin) and coxibs (celecoxib and etoricoxib) on LPS-stimulated microglial cell function (a worldwide accepted neuroinflammation model) were investigated, and the effects on COX-1/COX-2, cPGES mRNA and iNOS expression, PGE2 and NO production and NF-kB activation by IkBalpha phosphorylation were evaluated. The total suppression of the expressionof both COX-1 and COX-2 by their respective selective inhibitors occurred. NF-kB remained almost completely inactive in the presence of coxibs, as expected, and totally inactive in the presence of P6. P6 also markedly counteracted LPS enhancing cPGES mRNA expression and PGE2 production. Since COX-1 is predominantly localized in microglia, its high selective inhibition rather than COX-2 (by coxibs) is more likely to reduce neuroinflammation and has been further investigated as a potential therapeutic approach and prevention in neurodegenerative diseases with a marked inflammatory component.

Autore Pugliese

• Scilimati Antonio , Panaro Maria Antonietta , Perrone Maria Grazia , Vitale Paola , Calvello Rosa

Tutti gli autori

• CIANCIULLI A.;SCILIMATI A.;PANARO M.A.;PERRONE M.G.;VITALE P.;CALVELLO R.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2012

ISSN

1043-6618

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

31

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile