Activation of NF-κB pathway and TNF-α are involved in the cytotoxicity of anthrax lethal toxin in bovine BoMac macrophages.
Anthrax lethal toxin (LeTx) is an important virulence factor of Bacillus anthracis and causes illness and lethality for both animals and humans. Because species demonstrate varied sensitivity to anthrax intoxication, we investigated signaling pathways involved in anthrax LeTx cytotoxicity using a bovine macrophage cell line (BoMac). We found that bovine macrophages are sensitive to LeTx as displayed by a concentration-dependent increase in cell death. LeTx induced the degradation of I-κB and increased the nuclear translocation of NF-κB in BoMac cells. Blocking NF-κB activation with either chemical inhibitors or a dominant negative super-repressor I-κBαm eliminated LeTx-induced cell death. LeTx-induced production of TNF-α that contributed dramatically to cellular cytotoxicity. Inhibiting NF-κB activation eliminated TNF-α release and decreased cytotoxicity. The caspase pathway was also important for cytotoxicity as specific inhibitors abrogated LeTx-induced cell death. Taken together, our results show that activation of the NF-κB pathway and TNF-α production contribute to the cytotoxicity of anthrax LeTx in bovine macrophages.
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1971 Commonwealth Ave., St. Paul, MN 55108, USA.
Xudong
X
Liang
Chong Feng
CF
Gao
Mark S
MS
Rutherford
Yinduo
Y
Ji
D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001427:Bacterial Toxins / Q000633:toxicity*; D015153:Blotting, Western / Q000662:veterinary; D020169:Caspases / Q000502:physiology; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique / Q000662:veterinary; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology; D016328:NF-kappa B / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection / Q000662:veterinary; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C030325:anthrax toxin; D020169:Caspases