Dexamethasone Suppresses Tumor Necrosis Factor-α-Induced Apoptosis in Osteoblasts: Possible Role for Ceramide1

2000 
Ceramide has been proposed as a second messenger molecule implicated in a variety of biological processes, including apoptosis. Recently, it has been reported that tumor necrosis factor-α (TNF-α) activates the release of ceramide and that ceramide acts as a mediator for the TNF-α-induced stimulation of the binding affinity of nuclear factor-κB (NF-κB), a ubiquitous transcription factor of particular importance in immune and inflammatory responses. In this study we demonstrate that dexamethasone, which reduces the production of ceramide, significantly inhibits TNF-α-induced activation of NF-κB, c-Jun N-terminal kinase, also known as stress-activating protein kinase, caspase-3-like cysteine protease, redistribution of cytochrome c, and apoptosis in MC3T3E1 osteoblasts. Compared with TNF-α-induced JNK activation, ceramide elicits a more rapid activation of JNK within 30 min. C2-ceramide activates NF-κB and caspase-3 like protease to the same degree and with kinetics similar to those of TNF-α. This study prov...
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