Lipopolysaccharide Signals an Endothelial Apoptosis Pathway Through TNF Receptor-Associated Factor 6-Mediated Activation of c-Jun NH2-Terminal Kinase

摘要: Inflammatory mediators such as TNF and bacterial LPS do not cause significant apoptosis of endothelial cells unless the expression cytoprotective genes is blocked. In case TNF, transcription factor NF-kappaB conveys an important survival signal. contrast, even though can also activate NF-kappaB, this signal dispensable for LPS-inducible activity. intracellular signals are transmitted through a member Toll-like receptor family, TLR4. This family receptors transduces downstream molecule, TNFR-associated 6 (TRAF6). study, we demonstrate that C-terminal fragment TRAF6 (TRAF6-C) inhibits LPS-induced nuclear translocation c-Jun NH(2)-terminal kinase (JNK) activation in cells. p38 inhibited by TRAF6-C. TRAF6-C LPS-initiated apoptosis, but potentiates TNF-induced apoptosis. loss mitochondrial transmembrane potential, cytochrome c release, caspase all blocked We via JNK activation, since inhibition using dominant-negative mutant blocks reverse true. Hence, lies upstream response to stimulation.