Transcriptional responses of murine macrophages to the adenylate cyclase toxin of Bordetella pertussis.
Three different recombinant forms of CyaA were used to investigate transcriptional responses of murine bone marrow-derived macrophages (BMMs) using Affymetrix Mouse Genome GeneChips. These forms were enzymically active, invasive CyaA, non-enzymically active, invasive CyaA (CyaA*) and non-enzymically active, non-invasive CyaA (proCyaA*). BMMs, treated with 20 ng/ml of CyaA for 24h, showed over 1000 significant changes in gene transcription compared with control cells. CyaA caused an increase in transcription of many inflammatory genes and genes associated with various signalling cascades such as those involved in cyclic AMP-dependent protein kinase A signalling. Most strikingly, CyaA caused down-regulation of numerous genes involved in cell proliferation. CyaA* at 20 ng/ml significantly up-regulated the transcription of only twelve genes after 24h whereas proCyaA* at this concentration significantly increased the transcription of only two genes.
Cheung
Gordon Y C
GY
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow, UK. cheunggo@niaid.nih.gov
Dickinson
Paul
P
Sing
Garwin
G
Craigon
Marie
M
Ghazal
Peter
P
Parton
Roger
R
Coote
John G
JG
D037361:Adenylate Cyclase Toxin / Q000633:toxicity*; D000818:Animals; D001886:Bordetella pertussis / Q000276:immunology; D015536:Down-Regulation / Q000502:physiology*; D020869:Gene Expression Profiling; D005796:Genes / Q000502:physiology; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011994:Recombinant Proteins / Q000633:toxicity*; D015854:Up-Regulation / Q000502:physiology*
D037361:Adenylate Cyclase Toxin; D011994:Recombinant Proteins