Abstract
Apoptosis of matrix producing cells is common among many inflammatory diseases. The goal of the present study was to examine the apoptotic effects of tumor necrosis factor-α (TNF-α) on fibroblastic cells in vivo and to investigate the role of different caspases in this process. This was accomplished in vivo by subcutaneous injection of TNF-α in mice. The direct effects of TNF-α on fibroblast apoptosis were studied in vitro with normal diploid human fibroblasts. The results indicate that TNF-α in vivo induces apoptosis of fibroblasts. By RNase protection assay, we demonstrated that TNF-α stimulates expression of 12 apoptotic genes. Fluorometric studies demonstrated that TNF-α in vivo predominantly increased caspase-8 and -3 activity and by use of specific inhibitors, the activation of caspase-3 was shown to be initiated by caspase-8 with only a minor contribution from caspase-9. Thus, TNF-α acts to modulate the expression of many genes that favors apoptosis of fibroblastic cells, which is dependent mostly upon signaling through caspase-8.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 341-348 |
| Number of pages | 8 |
| Journal | Journal of Cellular Physiology |
| Volume | 201 |
| Issue number | 3 |
| DOIs | |
| State | Published - Dec 2004 |
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ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology
- Physiology
Cite this
TNF-α in vivo stimulates apoptosis in fibroblasts through caspase-8 activation and modulates the expression of pro-apoptotic genes. / Alikhani, Mani; Alikhani, Zoubin; Raptis, Markos; Graves, Dana T.
In: Journal of Cellular Physiology, Vol. 201, No. 3, 12.2004, p. 341-348.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TNF-α in vivo stimulates apoptosis in fibroblasts through caspase-8 activation and modulates the expression of pro-apoptotic genes
AU - Alikhani, Mani
AU - Alikhani, Zoubin
AU - Raptis, Markos
AU - Graves, Dana T.
PY - 2004/12
Y1 - 2004/12
N2 - Apoptosis of matrix producing cells is common among many inflammatory diseases. The goal of the present study was to examine the apoptotic effects of tumor necrosis factor-α (TNF-α) on fibroblastic cells in vivo and to investigate the role of different caspases in this process. This was accomplished in vivo by subcutaneous injection of TNF-α in mice. The direct effects of TNF-α on fibroblast apoptosis were studied in vitro with normal diploid human fibroblasts. The results indicate that TNF-α in vivo induces apoptosis of fibroblasts. By RNase protection assay, we demonstrated that TNF-α stimulates expression of 12 apoptotic genes. Fluorometric studies demonstrated that TNF-α in vivo predominantly increased caspase-8 and -3 activity and by use of specific inhibitors, the activation of caspase-3 was shown to be initiated by caspase-8 with only a minor contribution from caspase-9. Thus, TNF-α acts to modulate the expression of many genes that favors apoptosis of fibroblastic cells, which is dependent mostly upon signaling through caspase-8.
AB - Apoptosis of matrix producing cells is common among many inflammatory diseases. The goal of the present study was to examine the apoptotic effects of tumor necrosis factor-α (TNF-α) on fibroblastic cells in vivo and to investigate the role of different caspases in this process. This was accomplished in vivo by subcutaneous injection of TNF-α in mice. The direct effects of TNF-α on fibroblast apoptosis were studied in vitro with normal diploid human fibroblasts. The results indicate that TNF-α in vivo induces apoptosis of fibroblasts. By RNase protection assay, we demonstrated that TNF-α stimulates expression of 12 apoptotic genes. Fluorometric studies demonstrated that TNF-α in vivo predominantly increased caspase-8 and -3 activity and by use of specific inhibitors, the activation of caspase-3 was shown to be initiated by caspase-8 with only a minor contribution from caspase-9. Thus, TNF-α acts to modulate the expression of many genes that favors apoptosis of fibroblastic cells, which is dependent mostly upon signaling through caspase-8.
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U2 - 10.1002/jcp.20067
DO - 10.1002/jcp.20067
M3 - Article
VL - 201
SP - 341
EP - 348
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
IS - 3
ER -