Lack of cell-cycle-specific effects of recombinant tumor necrosis factor in vivo

1994 ◽  
Vol 39 (5) ◽  
pp. 337-341 ◽  
Author(s):  
Martin J�ckel ◽  
Petra K�pf-Maier ◽  
Robert Tausch-Treml
2000 ◽  
Vol 191 (7) ◽  
pp. 1095-1104 ◽  
Author(s):  
Kaimei Song ◽  
Yiguang Chen ◽  
Rüdiger Göke ◽  
Andreas Wilmen ◽  
Cheryl Seidel ◽  
...  

The tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces apoptosis of tumor cells but not normal cells; its role in normal nontransformed tissues is unknown. We report here that chronic blockade of TRAIL in mice exacerbated autoimmune arthritis, and that intraarticular TRAIL gene transfer ameliorated the disease. In vivo, TRAIL blockade led to profound hyperproliferation of synovial cells and arthritogenic lymphocytes and heightened the production of cytokines and autoantibodies. In vitro, TRAIL inhibited DNA synthesis and prevented cell cycle progression of lymphocytes. Interestingly, TRAIL had no effect on apoptosis of inflammatory cells either in vivo or in vitro. Thus, unlike other members of the tumor necrosis factor superfamily, TRAIL is a prototype inhibitor protein that inhibits autoimmune inflammation by blocking cell cycle progression.


2009 ◽  
Vol 43 (4) ◽  
pp. 286-296 ◽  
Author(s):  
E. Schell-Frederick ◽  
T. Tepass ◽  
G. Lorscheidt ◽  
M. Pfreundschuh ◽  
M. Schaadt ◽  
...  

1993 ◽  
Vol 265 (2) ◽  
pp. C365-C374 ◽  
Author(s):  
J. M. Wan ◽  
F. Fogt ◽  
B. R. Bistrian ◽  
N. W. Istfan

To determine the significance of protein breakdown in regulating tumor growth and to better understand the antitumor mechanism of tumor necrosis factor in vivo, we measured the effects of a 6-h constant intravenous infusion of human recombinant tumor necrosis factor-alpha (rHuTNF) on tumor protein metabolism and cell cycle kinetics in rats bearing the Walker-256 carcinosarcoma. Protein metabolism was investigated with the use of [14C]leucine infusion; estimates of tumor cell cycle kinetics were obtained in vivo by use of 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling and bivariate BrdUrd/DNA analysis by flow cytometry. Reduction in tumor growth by rHuTNF was associated with a dose-dependent increase in tumor proteolysis but no change in tumor protein synthesis. At the cellular level, rHuTNF had a significant cytostatic effect on G2/M cells and caused a marked decrease in the fraction of cells capable of BrdUrd uptake. Release of BrdUrd, an indicator of cell death, was noted in only 7.5% of tumor cells labeled at the beginning of rHuTNF infusion. These results suggest that either tumor protein breakdown may influence cell cycle activity by regulating cytoplasmic protein mass or that tumor proteolysis may be a compensatory mechanism for limiting cytoplasmic size when cellular division is interrupted suddenly.


2002 ◽  
Vol 20 (4) ◽  
pp. 499-508 ◽  
Author(s):  
Alexander H. van der Veen ◽  
Timo L. M. ten Hagen ◽  
Ann L. B. Seynhaeve ◽  
Alexander M. M. Eggermont

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