Transcriptional suppression of matrix metalloproteinase-2 gene expression in human astroglioma cells by TNF-alpha and IFN-gamma.
| Title: | Transcriptional suppression of matrix metalloproteinase-2 gene expression in human astroglioma cells by TNF-alpha and IFN-gamma. |
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| Authors: | Qin H; Department of Cell Biology, University of Alabama, Birmingham 35294, USA.; Moellinger JD; Wells A; Windsor LJ; Sun Y; Benveniste EN |
| Source: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1998 Dec 15; Vol. 161 (12), pp. 6664-73. |
| Publication Type: | Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: England NLM ID: 2985117R Publication Model: Print Cited Medium: Print ISSN: 0022-1767 (Print) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2025- : [Oxford] : Oxford University Press; Original Publication: Baltimore : Williams & Wilkins, c1950- |
| MeSH Terms: | Astrocytes/*drug effects ; Astrocytoma/*pathology ; Brain Neoplasms/*pathology ; Gelatinases/*biosynthesis ; Interferon-gamma/*pharmacology ; Metalloendopeptidases/*biosynthesis ; Neoplasm Proteins/*biosynthesis ; Tumor Necrosis Factor-alpha/*pharmacology; Astrocytes/enzymology ; Collagenases/biosynthesis ; Collagenases/genetics ; Cytokines/pharmacology ; Enzyme Induction/drug effects ; Gelatinases/genetics ; Gelatinases/physiology ; Metalloendopeptidases/genetics ; Metalloendopeptidases/physiology ; Neoplasm Proteins/genetics ; Neoplasm Proteins/physiology ; RNA, Messenger/biosynthesis ; Recombinant Proteins/pharmacology ; Tissue Inhibitor of Metalloproteinase-2/biosynthesis ; Tissue Inhibitor of Metalloproteinase-2/genetics ; Tissue Inhibitor of Metalloproteinase-2/pharmacology ; Frontal Lobe ; Humans ; Matrix Metalloproteinase 1 ; Matrix Metalloproteinase 2 ; Neoplasm Invasiveness ; Transcription, Genetic ; Tumor Cells, Cultured |
| 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-alpha and IFN-gamma 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-alpha and IFN-gamma is not due to destabilization of the MMP-2 message; rather, inhibition is mediated at the transcriptional level. Furthermore, TNF-alpha/IFN-gamma 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-alpha and IFN-gamma may have beneficial effects in attenuating astroglioma invasive properties. |
| Grant Information: | GM54739 United States GM NIGMS NIH HHS; MH55795 United States MH NIMH NIH HHS; NS34856 United States NS NINDS NIH HHS |
| Substance Nomenclature: | 0 (Cytokines); 0 (Neoplasm Proteins); 0 (RNA, Messenger); 0 (Recombinant Proteins); 0 (Tumor Necrosis Factor-alpha); 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2); 82115-62-6 (Interferon-gamma); EC 3.4.24.- (Collagenases); EC 3.4.24.- (Gelatinases); EC 3.4.24.- (Metalloendopeptidases); EC 3.4.24.24 (Matrix Metalloproteinase 2); EC 3.4.24.7 (Matrix Metalloproteinase 1) |
| Entry Date(s): | Date Created: 19981223 Date Completed: 19990122 Latest Revision: 20111117 |
| Update Code: | 20260130 |
| PMID: | 9862695 |
| Database: | MEDLINE |
Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.