Sp1 and Sp3 Transcription Factors Mediate Interleukin-1β Down-regulation of Human Type II Collagen Gene Expression in Articular Chondrocytes - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2003

Sp1 and Sp3 Transcription Factors Mediate Interleukin-1β Down-regulation of Human Type II Collagen Gene Expression in Articular Chondrocytes

Résumé

Interleukin-1 beta (IL-1 beta) is a pleiotropic cytokine that was shown to inhibit the biosynthesis of articular cartilage components. Here we demonstrate that IL-1 beta inhibits the production of newly synthesized collagens in proliferating rabbit articular chondrocytes and that this effect is accompanied by a decrease in the steady-state levels of type II collagen mRNA. IL-1 beta down-regulates COL2A1 gene transcription through a -41/-33 bp sequence that binds a multimeric complex including Sp1 and Sp3 transcription factors. Specificity of IL-1 beta effects on COL2A1 promoter activity was demonstrated in experiments in which transfection of a wild type -50/+1 sequence of COL2A1 promoter as a decoy oligonucleotide abolished the IL-1 beta inhibition of a -63/+47 COL2A1-mediated transcription. By contrast, transfection of the related oligonucleotide harboring a targeted mutation in the -41/-33 sequence did not modify the negative effect the cytokine. Because we demonstrated previously that Sp1 was a strong activator of COL2A1 gene expression via the -63/+1 promoter region, whereas Sp3 overexpression blocked Sp1-induced promoter activity and inhibited COL2A1 gene transcription, we conclude that IL-1 beta down-regulation of that gene, as we found previously for transforming growth factor-beta 1, is mediated by an increase in the Sp3/Sp1 ratio. Moreover, IL-1 beta increased steady-state levels of Sp1 and Sp3 mRNAs, whereas it enhanced Sp3 protein expression and inhibited Sp1 protein biosynthesis. Nevertheless, IL-1 beta decreased the binding activity of both Sp1 and Sp3 to the 63-bp short COL2A1 promoter, suggesting that the cytokine exerts a post-transcriptional regulatory mechanism on Sp1 and Sp3 gene expressions. Altogether, these data indicate that modulation of Sp3/Sp1 ratio in cartilage could be a potential target to prevent or limit the tissue degradation.

Dates et versions

hal-03838509 , version 1 (03-11-2022)

Identifiants

Citer

Christos Chadjichristos, Chafik Ghayor, Magdalini Kypriotou, Grégoire Martin, Renard Emmanuelle, et al.. Sp1 and Sp3 Transcription Factors Mediate Interleukin-1β Down-regulation of Human Type II Collagen Gene Expression in Articular Chondrocytes. Journal of Biological Chemistry, 2003, 278 (41), pp.39762-39772. ⟨10.1074/jbc.M303541200⟩. ⟨hal-03838509⟩

Collections

INSERM CNRS
9 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More