Abstract
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.
Original language | English (US) |
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Pages (from-to) | 111-117 |
Number of pages | 7 |
Journal | Veterinary Microbiology |
Volume | 146 |
Issue number | 1-2 |
DOIs | |
State | Published - Nov 20 2010 |
Bibliographical note
Funding Information:We thank Dr. Meiying Yan for technical assistance, Dr. Nicholas Duesbery for providing lethal toxins, and Drs. Karin Matchett and Martin Rosenberg, and reviewers for critical reading the manuscript. This work is supported by (to Y. Ji) provided by the College of Veterinary Medicine at the University of Minnesota .
Keywords
- Anthrax lethal toxin
- Bovine macrophage
- Cytotoxicity
- NF-κB
- TNF-α