Interleukin-1β upregulates MMP-9 expression in stromal cells of human giant cell tumor of bone

Velidi H. Rao, Rakesh K Singh, Duane C. Delimont, G. Bradley Schaefer, Julia A. Bridge, James R. Neff, Warren G. Sanger, Joshua W. Sappenfield, Bruce A. Buehler, Richard H. Finnell

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Abstract

Giant cell tumor (GCT) of bone is a progressive, potentially malignant process that destroys skeletal tissue. It consists of multinucleated giant cells, which are hypothesized to be derived from a monocyte/macrophage lineage and mononuclear stromal cells, and the precise relationship of these cells is not fully understood. Recently, we demonstrated that the production of matrix metalloproteinase-9 (MMP-9) in GCT stromal cells is regulated by certain factor(s) secreted by the multinucleated giant cells. In the present study, we evaluated for the presence of interleukin-1β (IL-1β) and attempted to establish its possible role for the induction of MMP-9 in GCT stromal cells. Using enzyme-linked immunosorbent assay (ELISA), we have demonstrated that the primary GCT cultures secrete both IL-1β and MMP-9. The addition of monoclonal antibody (mAb) against IL-1β partially abrogated, but did not abolish, MMP-9 expression. Our results on gelatin zymography, reverse transcriptase-polymerase chain reaction (RT-PCR), and immunofluorescence showed that GCT stromal cells did not express MMP-9, although treatment with IL-1β induced MMP-9 expression in a dose-dependent manner, and the secretion peaked 24 h after stimulation and then plateaued. Studies with cycloheximide, a protein synthesis inhibitor, demonstrated that de novo protein synthesis is required for IL-1β induced MMP-9 expression. Moreover, nuclear run-on analysis has revealed that IL-1β significantly increased MMP-9 gene transcription in GCT stromal cells. The data suggest that IL-1β secreted by the multinucleated giant cells in GCT may be one of the factors responsible for the induction of MMP-9 at the transcriptional level in GCT stromal cells in vivo. We conclude that GCT has a self-stimulatory system for the production of MMP-9, and the ability of stromal cells to produce MMP-9 with appropriate stimuli, such as IL-1β, and possibly in concert with other cytokines may contribute to the aggressive and potentially malignant behavior of GCT.

Original languageEnglish (US)
Pages (from-to)1207-1217
Number of pages11
JournalJournal of Interferon and Cytokine Research
Volume19
Issue number10
DOIs
StatePublished - Jan 1 1999

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Giant Cell Tumor of Bone
Matrix Metalloproteinase 9
Giant Cell Tumors
Stromal Cells
Interleukin-1
Up-Regulation
Giant Cells
Protein Synthesis Inhibitors
Gelatin
Cycloheximide
Reverse Transcriptase Polymerase Chain Reaction
Fluorescent Antibody Technique

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

Cite this

Interleukin-1β upregulates MMP-9 expression in stromal cells of human giant cell tumor of bone. / Rao, Velidi H.; Singh, Rakesh K; Delimont, Duane C.; Schaefer, G. Bradley; Bridge, Julia A.; Neff, James R.; Sanger, Warren G.; Sappenfield, Joshua W.; Buehler, Bruce A.; Finnell, Richard H.

In: Journal of Interferon and Cytokine Research, Vol. 19, No. 10, 01.01.1999, p. 1207-1217.

Research output: Contribution to journalArticle

Rao, VH, Singh, RK, Delimont, DC, Schaefer, GB, Bridge, JA, Neff, JR, Sanger, WG, Sappenfield, JW, Buehler, BA & Finnell, RH 1999, 'Interleukin-1β upregulates MMP-9 expression in stromal cells of human giant cell tumor of bone', Journal of Interferon and Cytokine Research, vol. 19, no. 10, pp. 1207-1217. https://doi.org/10.1089/107999099313154
Rao, Velidi H. ; Singh, Rakesh K ; Delimont, Duane C. ; Schaefer, G. Bradley ; Bridge, Julia A. ; Neff, James R. ; Sanger, Warren G. ; Sappenfield, Joshua W. ; Buehler, Bruce A. ; Finnell, Richard H. / Interleukin-1β upregulates MMP-9 expression in stromal cells of human giant cell tumor of bone. In: Journal of Interferon and Cytokine Research. 1999 ; Vol. 19, No. 10. pp. 1207-1217.
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AU - Schaefer, G. Bradley

AU - Bridge, Julia A.

AU - Neff, James R.

AU - Sanger, Warren G.

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