Chlamydia pneumoniae activates nuclear factor kappaB and activator protein 1 in human vascular smooth muscle and induces cellular proliferation.
BACKGROUND
Observational data strongly suggest an association between Chlamydia pneumoniae and atherosclerotic cardiovascular disease. However, few studies have mechanistically linked C. pneumoniae to vascular remodeling. The purpose of the present study was to examine the mechanistic relationship between C. pneumoniae and human vascular smooth muscle cell (VSMC) physiology. We sought to determine the influence of human VSMC infection by C. pneumoniae on (1) VSMC proliferation and (2) activation of the proinflammatory and proliferative transcription factors nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1).


METHODS
C. pneumoniae was grown and isolated from Hep 2 cells. Human aortic VSMCs were inoculated with C. pneumoniae in the presence and absence of the azalide antibiotic azithromycin. Cell proliferation was assayed by direct cell counting 48 h following infection. Two hours following infection, nuclear extracts were isolated, and activation of both NF-kappaB and AP-1 was assessed by electrophoretic mobility shift assay.


RESULTS
Compared with control, C. pneumoniae infection stimulated VSMC proliferation (P < 0.05) and induced both NF-kappaB and AP-1 DNA binding activity. These effects were eliminated by concurrent treatment with azithromycin.


CONCLUSIONS
VSMC infection with C. pneumoniae activates proliferative intracellular signals and stimulates cell growth. These data implicate C. pneumoniae as a pathogenic mediator and a potential therapeutic target in the prevention of atherosclerotic disease.
Miller
S A
SA
Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Selzman
C H
CH
Shames
B D
BD
Barton
H A
HA
Johnson
S M
SM
Harken
A H
AH
D001161:Arteriosclerosis / Q000209:etiology*; D017963:Azithromycin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D004247:DNA / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000382:microbiology*; D016328:NF-kappa B / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D016328:NF-kappa B; D018808:Transcription Factor AP-1; D017963:Azithromycin; D004247:DNA