Tumor necrosis factor-alpha enhances Haemophilus somnus lipooligosaccharide-induced apoptosis of bovine endothelial cells

Abstract

Haemophilus somnus lipooligosaccharide (LOS)-induced apoptosis of bovine pulmonary artery endothelial cells has been shown previously to be dependent on capsase-8 activation. Activation of caspase-8 can occur via a death receptor-dependent mechanism (e.g., TNF-α binding to TNF-α receptor 1 (TNF-R1)). In this study, we tested the hypothesis that TNF-α can enhance LOS-induced apoptosis of bovine endothelial cells. Addition of exogenous recombinant human TNF-α alone failed to cause apoptosis, or enhance LOS-induced apoptosis, of bovine endothelial cells. However, blocking de novo protein synthesis by addition of cycloheximide significantly enhanced apoptosis of bovine endothelial cells by TNF-α, LOS or TNF-α and LOS in combination. Conversely, addition of soluble recombinant human (sTNF-R1) diminished LOS-induced apoptosis. Overall, these data suggest that LOS-mediated apoptosis may be due, in part, to activation of a TNR-R1-dependent death pathway.