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 language | English (US) |
|---|---|
| Pages (from-to) | 1207-1217 |
| Number of pages | 11 |
| Journal | Journal of Interferon and Cytokine Research |
| Volume | 19 |
| Issue number | 10 |
| DOIs | |
| State | Published - Jan 1 1999 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Interleukin-1β upregulates MMP-9 expression in stromal cells of human giant cell tumor of bone
AU - Rao, Velidi H.
AU - Singh, Rakesh K
AU - Delimont, Duane C.
AU - Schaefer, G. Bradley
AU - Bridge, Julia A.
AU - Neff, James R.
AU - Sanger, Warren G.
AU - Sappenfield, Joshua W.
AU - Buehler, Bruce A.
AU - Finnell, Richard H.
PY - 1999/1/1
Y1 - 1999/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032589804&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032589804&partnerID=8YFLogxK
U2 - 10.1089/107999099313154
DO - 10.1089/107999099313154
M3 - Article
C2 - 10547161
AN - SCOPUS:0032589804
VL - 19
SP - 1207
EP - 1217
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
SN - 1079-9907
IS - 10
ER -