Differential expression of the Fas-Fas ligand system on cytokine-induced apoptotic cell death in mouse osteoblastic cells.
Apoptotic signalling, particularly in the Fas-Fas ligand (FasL) system, was studied in a mouse osteoblastic cell line, MC3T3-E1. A combination of the cytokines tumour necrosis factor-alpha, interleukin-1beta and interferon-gamma activated the Fas-FasL-dependent cell-death system. The cytokines caused significant enhancement of Fas mRNA and Fas protein, and led to apoptotic cell death. Western blot demonstrated that FasL protein was continuously present in MC3T3-E1 cells, although the cytokines had no effect on the induction of FasL. Exogenous FasL caused a decrease in cell viability and a large increase in apoptotic cell death in cells pre-treated with cytokines, indicating that the Fas-FasL system has the potential to cause apoptosis in osteoblastic cells. Treatment with anti-Fas IgG (antagonistic antibody) inhibited the DNA fragmentation induced by cytokines in a dose-dependent manner, suggesting that cytokine-induced Fas may cause apoptotic cell death in MC3T3-E1 cells. Taken together, these findings show that cytokine-induced apoptotic cell death was mediated by the autocrine or paracrine Fas-FasL system in mouse osteoblastic cells, and suggest that cytokine-induced apoptosis could have an important role in localised bone destruction associated with inflammatory bone diseases such as periodontal disease.
Department of Endodontics, School of Dentistry, Aichi-Gakuin University, Nagoya 464-8651, Japan.
Nobuaki
N
Ozeki
Makio
M
Mogi
Hiroshi
H
Nakamura
Akifumi
A
Togari
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D015153:Blotting, Western; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D015870:Gene Expression; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007375:Interleukin-1; D008024:Ligands; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C411023:anti-Fas monoclonal antibody; D007371:Interferon-gamma