Protein kinase C-zeta regulates transcription of the matrix metalloproteinase-9 gene induced by IL-1 and TNF-alpha in glioma cells via NF-kappa B

Estève, Pierre-Olivier; Chicoine, Eric; Robledo, Olivier; Aoudjit, Fawzi; Descoteaux, Albert ORCID: https://orcid.org/0000-0002-0633-5309; Potworowski, Edouard F. et St-Pierre, Yves ORCID: https://orcid.org/0000-0002-1948-2041 (2002). Protein kinase C-zeta regulates transcription of the matrix metalloproteinase-9 gene induced by IL-1 and TNF-alpha in glioma cells via NF-kappa B Journal of Biological Chemistry , vol. 277 , nº 38. pp. 35150-35155. DOI: 10.1074/jbc.M108600200.

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Résumé

The regulation of matrix metalloproteinase-9 (MMP-9) expression in glioma cells is one of the key processes in tumor invasion through the brain extracellular matrix. Although some studies have demonstrated the implication of classic protein kinase C (PKC) isoforms in the regulation of AMP-9 production by phorbol esters or lipopolysaccharide, the involvement of specific PKC isoforms in the signaling pathways leading to MMP-9 expression by inflammatory cytokines remains unclear. Here we report that the atypical PKC-zeta isoform participates in the induction of AMP-9 expression by interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) in rat C6 glioma cells. Indeed, zymography and semi-quantitative reverse transcriptase-PCR analysis showed that pretreatment of C6 cells with PKC-zeta pseudosubstrate abolished AMP-9 activity and gene expression induced by IL-1 or TNIF-alpha. Accordingly, IL-1 and TNF-alpha were able to induce PKC-zeta activity, as demonstrated by in vitro kinase assay using immunoprecipitated PKC-zeta. Furthermore, stable C6 clones overexpressing PKC-zeta, but not PKC-epsilon, displayed an up-regulation of NMP-9 constitutive expression as well as an increase of mmp-9 promoter activity. These processes were inhibited by an NF-kappaB-blocking peptide and completely prevented by NF-kappaB-binding site mutation in the mmp-9 promoter. Taken together, these results indicate that PKC-zeta plays a key role in the regulation of MMP-9 expression in C6 glioma cells through NF-kappaB.

Type de document:	Article
Mots-clés libres:	-
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	03 mars 2025 20:56
Dernière modification:	03 mars 2025 20:56
URI:	https://espace.inrs.ca/id/eprint/14651

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