Transcriptional suppression of matrix metalloproteinase-2 gene expression in human astroglioma cells by TNF-α and IFN-γ1

Hongwei Qin, Jason D. Moellinger, Alan Wells, L. Jack Windsor, Yi Sun, Etty N. Benveniste

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that function in the turnover of extracellular matrix components during development. In addition, MMPs also contribute to pathological conditions associated with inflammation, angiogenesis, and tumor invasion. A 72-kDa type IV collagenase, also referred to as gelatinase A or MMP-2, has been proposed to potentiate the invasion and metastasis of malignant tumors. In particular, MMP-2 activity has been shown to constitute an important component of human astroglioma invasion. We investigated the influence of various cytokines, both proinflammatory and immunosuppressive, on MMP-2 gene expression in two human astroglioma cell lines (U251-MG and CRT). Our results indicate that the cell lines constitutively express high levels of MMP-2 mRNA, protein, and bioactivity as assessed by ribonuclease protection assay, immunoblotting, and zymography assays, respectively. The proinflammatory cytokines TNF-α and IFN-γ individually can inhibit constitutive MMP-2 expression, and function in an additive manner for near- complete inhibition of MMP-2 expression. Inhibition of MMP-2 mRNA levels by TNF-α and IFN-γ is not due to destabilization of the MMP-2 message; rather, inhibition is mediated at the transcriptional level. Furthermore, TNF- α/IFN-γ inhibition of MMP-2 expression results in decreased invasiveness of the human astroglioma cells through an extracellular matrix. These results raise the possibility that TNF-α and IFN-γ may have beneficial effects in attenuating astroglioma invasive properties.

Original languageEnglish (US)
Pages (from-to)6664-6673
Number of pages10
JournalJournal of Immunology
Volume161
Issue number12
StatePublished - Dec 15 1998
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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