Murine macrophage transcriptional and functional responses to Bacillus anthracis edema toxin

Jason Comer, Cristi L. Galindo, Fan Zhang, Autumn M. Wenglikowski, Katie L. Bush, Harold R. Garner, Johnny Peterson, Ashok Chopra

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Edema toxin (EdTx), which is a combination of edema factor and a binding moiety (protective antigen), is produced by Bacillus anthracis, the etiological agent of anthrax. EdTx is an adenylyl cyclase enzyme that converts adenosine triphosphate to adenosine-3′,5′-monophosphate, resulting in interstitial edema seen in anthrax patients. We used GeneChip analysis to examine global transcriptional profiles of EdTx-treated RAW 264.7 murine macrophage-like cells and identified 71 and 259 genes whose expression was significantly altered by the toxin at 3 and 6 h, respectively. Alteration in the expression levels of selected genes was confirmed by real time-reverse transcriptase polymerase chain reaction. The genes with up-regulated expression in macrophages in response to EdTx-treatment were known to be involved in inflammatory responses, regulation of apoptosis, adhesion, immune cell activation, and transcription regulation. Additionally, GeneChip analysis results implied that EdTx-induced activation of activator protein-1 (AP-1) and CAAAT/enhancer-binding protein-beta (C/EBP-β). Gel shift assays were therefore performed, and an increase in the activities of both of these transcription factors was observed within 30 min. EdTx also inhibited tumor necrosis factor alpha production and crippled the phagocytic ability of the macrophages. This is the first report detailing the host cell global transcriptional responses to EdTx.

Original languageEnglish (US)
Pages (from-to)96-110
Number of pages15
JournalMicrobial Pathogenesis
Volume41
Issue number2-3
DOIs
StatePublished - Aug 2006

Fingerprint

Edema
Macrophages
Anthrax
Bacillus anthracis
anthrax toxin
Transcription Factor AP-1
Reverse Transcriptase Polymerase Chain Reaction
Adenylyl Cyclases
Cell Adhesion
Transcriptional Activation
Genes
Carrier Proteins
Transcription Factors
Tumor Necrosis Factor-alpha
Gels
Apoptosis
Gene Expression
Antigens
Enzymes

Keywords

  • Bacillus anthracis
  • cAMP
  • Cytokine production
  • Edema toxin
  • Gel shift
  • Macrophages
  • Microarrays
  • Phagocytosis

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Cite this

Murine macrophage transcriptional and functional responses to Bacillus anthracis edema toxin. / Comer, Jason; Galindo, Cristi L.; Zhang, Fan; Wenglikowski, Autumn M.; Bush, Katie L.; Garner, Harold R.; Peterson, Johnny; Chopra, Ashok.

In: Microbial Pathogenesis, Vol. 41, No. 2-3, 08.2006, p. 96-110.

Research output: Contribution to journalArticle

Comer, Jason ; Galindo, Cristi L. ; Zhang, Fan ; Wenglikowski, Autumn M. ; Bush, Katie L. ; Garner, Harold R. ; Peterson, Johnny ; Chopra, Ashok. / Murine macrophage transcriptional and functional responses to Bacillus anthracis edema toxin. In: Microbial Pathogenesis. 2006 ; Vol. 41, No. 2-3. pp. 96-110.
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