A Trifluoromethyl Analogue of Celecoxib Exerts Beneficial Effects in Neuroinflammation
Data(s) |
11/01/2014
11/01/2014
11/12/2013
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Resumo |
15 p. Celecoxib is a selective cyclooxygenase-2 (COX2) inhibitor. We have previously shown that celecoxib inhibits experimental autoimmune encephalomyelitis (EAE) in COX-2-deficient mice, suggestive for a mode of action involving COX2-independent pathways. In the present study, we tested the effect of a trifluoromethyl analogue of celecoxib (TFM-C) with 205-fold lower COX-2 inhibitory activity in two models of neuroinflammation, i.e. cerebellar organotypic cultures challenged with LPS and the EAE mouse model for multiple sclerosis. TFM-C inhibited secretion of IL-1β, IL-12 and IL-17, enhanced that of TNF-α and RANTES, reduced neuronal axonal damage and protected from oxidative stress in the organotypic model. TFM-C blocked TNF-α release in microglial cells through a process involving intracellular retention, but induced TNF-α secretion in primary astrocyte cultures. Finally, we demonstrate that TFM-C and celecoxib ameliorated EAE with equal potency. This coincided with reduced secretion of IL-17 and IFN-γ by MOG-reactive T-cells and of IL-23 and inflammatory cytokines by bone marrow-derived dendritic cells. Our study reveals that non-coxib analogues of celecoxib may have translational value in the treatment of neuro-inflammatory conditions. |
Identificador |
PLoS ONE 8(12) : (2013) // e83119 1932-6203 http://hdl.handle.net/10810/11193 10.1371/journal.pone.0083119 |
Idioma(s) |
eng |
Publicador |
Public Library of Science |
Relação |
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0083119 |
Direitos |
© 2013 di Penta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. info:eu-repo/semantics/openAccess |
Palavras-Chave | #astrocytes #central nervous system #cytokines #enzyme-linked immunoassays #membrane proteins #microglial cells #secretion #T cells |
Tipo |
info:eu-repo/semantics/article |