Institution: | aDepartment of Pathobiological Sciences, University of Wisconsin, 4174 Veterinary Medicine Building, 2015 Linden Dr., Madison, WI 53706, USA bCenter for Molecular Medicine and Infectious Diseases, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0342, USA |
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- binding to TNF- receptor 1 (TNF-R1)). In this study, we tested the hypothesis that TNF- can enhance LOS-induced apoptosis of bovine endothelial cells. Addition of exogenous recombinant human TNF- 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-, LOS or TNF- 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. |