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. Windsor, Yi Sun, Etty N. Benveniste

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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

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Matrix Metalloproteinase 2
Astrocytoma
Gene Expression
Matrix Metalloproteinases
Extracellular Matrix
Cytokines
Cell Line
Endopeptidases
Messenger RNA
Immunosuppressive Agents
Ribonucleases
Immunoblotting
Zinc
Neoplasms
Neoplasm Metastasis
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

Transcriptional suppression of matrix metalloproteinase-2 gene expression in human astroglioma cells by TNF-α and IFN-γ1 . / Qin, Hongwei; Moellinger, Jason D.; Wells, Alan; Windsor, L.; Sun, Yi; Benveniste, Etty N.

In: Journal of Immunology, Vol. 161, No. 12, 15.12.1998, p. 6664-6673.

Research output: Contribution to journalArticle

Qin, Hongwei ; Moellinger, Jason D. ; Wells, Alan ; Windsor, L. ; Sun, Yi ; Benveniste, Etty N. / Transcriptional suppression of matrix metalloproteinase-2 gene expression in human astroglioma cells by TNF-α and IFN-γ1 In: Journal of Immunology. 1998 ; Vol. 161, No. 12. pp. 6664-6673.
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AU - Benveniste, Etty N.

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