Activation of NF-κB pathway and TNF-α are involved in the cytotoxicity of anthrax lethal toxin in bovine BoMac macrophages

Xudong Liang, Chong Feng Gao, Mark S. Rutherford, Yinduo Ji

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 languageEnglish (US)
Pages (from-to)111-117
Number of pages7
JournalVeterinary Microbiology
Volume146
Issue number1-2
DOIs
StatePublished - Nov 20 2010

Keywords

  • Anthrax lethal toxin
  • Bovine macrophage
  • Cytotoxicity
  • NF-κB
  • TNF-α

Fingerprint Dive into the research topics of 'Activation of NF-κB pathway and TNF-α are involved in the cytotoxicity of anthrax lethal toxin in bovine BoMac macrophages'. Together they form a unique fingerprint.

Cite this