Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/7965
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dc.contributor.authorMendes, A. Ferreira-
dc.contributor.authorCaramona, M. M.-
dc.contributor.authorCarvalho, A. P.-
dc.contributor.authorLopes, M. C.-
dc.date.accessioned2009-02-17T10:49:03Z-
dc.date.available2009-02-17T10:49:03Z-
dc.date.issued2003en_US
dc.identifier.citationCell Biology and Toxicology. 19:4 (2003) 203-214en_US
dc.identifier.urihttps://hdl.handle.net/10316/7965-
dc.description.abstractThe pro-inflammatory cytokine interleukin-1ß (IL-1) induces articular chondrocytes to produce reactive oxygen species (ROS), including hydrogen peroxide (H2O2), which mediate some IL-1-induced responses. This study aimed at elucidating the role of ROS, particularly H2O2, in mediating IL-1-induced activation of the transcription factor activator protein-1 (AP-1) in primary cultures of articular chondrocytes. AP-1 may function either as an inducer or as a repressor of the inducible nitric oxide synthase (iNOS) gene promoter. Since we observed that AP-1 is not required for iNOS expression in chondrocytes, we also investigated whether it is a repressor of this gene. The results of electrophoretic mobility shift assays showed that both IL-1 and H2O2 activated AP-1 and that inhibition of IL-1-induced ROS production abrogated AP-1 activation. The AP-1 complexes, induced by either IL-1 or H2O2, contained c-Fos/c-Jun and c-Fos/JunD heterodimers, but IL-1 activated AP-1 with a kinetics slower than that observed with H2O2. Pre-activation of AP-1, before stimulation of the cells with IL-1, did not inhibit iNOS mRNA and protein synthesis, relative to cells treated with IL-1 alone. These results indicate that H2O2 is a major mediator of IL-1-induced AP-1 activation in articular chondrocytes and that inhibition of ROS production is an effective strategy to block this IL-1-induced response. This study also identifies c-Fos/c-Jun and c-Fos/JunD heterodimers as the AP-1 transcription factors induced by IL-1, which, although not involved in the transcriptional regulation of the iNOS gene, may be important for the regulation of other genes also relevant in arthritic diseases, namely the collagenase-1 and IL-8 genes.en_US
dc.language.isoengeng
dc.rightsopenAccesseng
dc.titleHydrogen peroxide mediates interleukin-1ß-induced AP-1 activation in articular chondrocytes: Implications for the regulation of iNOS expressionen_US
dc.typearticleen_US
dc.identifier.doi10.1023/B:CBTO.0000003730.21261.faen_US
item.fulltextCom Texto completo-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextopen-
item.languageiso639-1en-
item.openairetypearticle-
item.cerifentitytypePublications-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0001-5511-7132-
crisitem.author.orcid0000-0003-1950-9360-
Appears in Collections:FFUC- Artigos em Revistas Internacionais
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