Autor(es):
Rosa, Susana C. 
; Judas, F. ; Lopes, M. C. ; Mendes, A. F.
Data: 2008
Identificador Persistente: http://hdl.handle.net/10316/11790
Origem: Estudo Geral - Universidade de Coimbra
Assunto(s): Condrócitos; Interleucina 1-b; NF-jB; Óxido nítrico; Osteoartrite; Degradação das proteínas; Sintase do óxido nítrico neuronal; Sintase do óxido nítrico indusível
Descrição
To elucidate the role of endogenous inducible nitric oxide (NO) on the regulation of NF-jB activity in
human chondrocytes, we evaluated (i) the pattern of expression of the neuronal (nNOS) and inducible
(iNOS) NO synthase isoforms and the basal NF-jB activity in normal and osteoarthritic (OA) human chondrocytes,
(ii) the role of cytokines and growth factors in modulating the protein levels of the two NOS
isoforms, and (iii) the effect of inhibiting endogenous inducible NO production on the ability of interleukin-
1b (IL-1) to induce NF-jB activation. nNOS was more frequently expressed in normal than in OA
chondrocytes, whereas the opposite was found for iNOS. IL-1 induced the degradation of both enzymes,
but iNOS disappeared more rapidly. Although IjB-a was present in all the normal samples and in the
majority of the OA samples, NF-jB–DNA binding activity in OA chondrocytes was increased approximately
twofold relatively to normal cells. Addition of a NOS inhibitor, after induction of iNOS expression,
induced IjB-a degradation and potenciated the effect of IL-1, indicating that endogenous inducible NO
inhibits NF-jB activation. Taken together, these findings favor an inhibitory role of high NO levels on
the regulation of NF-jB activation in chondrocytes, indicating that NF-jB activity is regulated, at least
in part, by the balanced production of NO resulting from a dynamic process that, at any given moment,
determines the availability of the constitutive and inducible NOS isoforms. Moreover, the down-regulatory
role of NO on NF-jB activation warrants caution as to the possible utilization of NO inhibitors in the
therapy of OA. a Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal
b Faculty of Pharmacy, University of Coimbra, 3000-295 Coimbra, Portugal
c Orthopedics Department, University Hospital of Coimbra, Coimbra, Portugal
d Faculty of Medicine, University of Coimbra, Coimbra, Portugal
www.elsevier.com/ locate/yniox
