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Sp1 and Sp3 transcription factors mediate interleukin-1 beta down-regulation of human type II collagen gene expression in articular chondrocytes.
J Biol Chem. 2003 Oct 10; 278(41):39762-72.JB

Abstract

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.

Authors+Show Affiliations

Laboratoire de Biochimie du Tissu Conjonctif, Faculté de Médecine, CHU Niveau 3, Avenue de la Côte de Nacre, Caen Cedex 14032, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12888570

Citation

Chadjichristos, Christos, et al. "Sp1 and Sp3 Transcription Factors Mediate Interleukin-1 Beta Down-regulation of Human Type II Collagen Gene Expression in Articular Chondrocytes." The Journal of Biological Chemistry, vol. 278, no. 41, 2003, pp. 39762-72.
Chadjichristos C, Ghayor C, Kypriotou M, et al. Sp1 and Sp3 transcription factors mediate interleukin-1 beta down-regulation of human type II collagen gene expression in articular chondrocytes. J Biol Chem. 2003;278(41):39762-72.
Chadjichristos, C., Ghayor, C., Kypriotou, M., Martin, G., Renard, E., Ala-Kokko, L., Suske, G., de Crombrugghe, B., Pujol, J. P., & Galéra, P. (2003). Sp1 and Sp3 transcription factors mediate interleukin-1 beta down-regulation of human type II collagen gene expression in articular chondrocytes. The Journal of Biological Chemistry, 278(41), 39762-72.
Chadjichristos C, et al. Sp1 and Sp3 Transcription Factors Mediate Interleukin-1 Beta Down-regulation of Human Type II Collagen Gene Expression in Articular Chondrocytes. J Biol Chem. 2003 Oct 10;278(41):39762-72. PubMed PMID: 12888570.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sp1 and Sp3 transcription factors mediate interleukin-1 beta down-regulation of human type II collagen gene expression in articular chondrocytes. AU - Chadjichristos,Christos, AU - Ghayor,Chafik, AU - Kypriotou,Magdalini, AU - Martin,Grégoire, AU - Renard,Emmanuelle, AU - Ala-Kokko,Leena, AU - Suske,Gunthram, AU - de Crombrugghe,Benoit, AU - Pujol,Jean-Pierre, AU - Galéra,Philippe, Y1 - 2003/07/29/ PY - 2003/7/31/pubmed PY - 2003/12/3/medline PY - 2003/7/31/entrez SP - 39762 EP - 72 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 278 IS - 41 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/12888570/Sp1_and_Sp3_transcription_factors_mediate_interleukin_1_beta_down_regulation_of_human_type_II_collagen_gene_expression_in_articular_chondrocytes_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=12888570 DB - PRIME DP - Unbound Medicine ER -