cDNA array analysis of altered gene expression in human endothelial cells in response to Chlamydia pneumoniae infection

Strong epidemiological and pathological evidence supports a role for Chlamy dia pneumoniae infection in atherosclerosis and human coronary heart diseas e, Animal models have shown that C, pneumoniae disseminates hematogenously in infected monocytes and macrophages, while in vitro data suggest that inf ected macrophages can transmit C, pneumoniae infection directly to endothel ial cells, Endothelial cells may be key in vivo targets for C, pneumoniae i nfection; given that these cells are important in regulating the dynamics o f the vessel wall, we used cDNA microarrays to study the transcriptional re sponse of endothelial cells to infection with C, pneumoniae, cDNA arrays we re used to characterize the mRNA expression profiles for 268 human genes fo llowing infection with C, pneumoniae, which were compared to mRNA profiles of uninfected cells. Selected genes of interest were further investigated b y reverse transcription-PCR throughout a 24-h period of infection. C, pneum oniae infection upregulated mRNA expression for approximately 20 (8%) of th e genes studied. Genes coding for cytokines (interleukin-l), chemokines (mo nocyte chemotactic protein 1 and interleukin-8), and cellular growth factor s (heparin-binding epidermal-like growth factor, basic fibroblast growth fa ctor, and platelet-derived growth factor B chain) were the most prominently upregulated, In addition to these families of genes, increases in mRNA lev els for intracellular kinases and cell surface receptors with signal transd uction activities were observed, Time course experiments showed that mRNA l evels were upregulated within 2 h following infection, These results expand our knowledge of the response of endothelial cells to C, pneumoniae by fur ther defining the repertoire of C, pneumoniae-inducible genes and provide n ew insight into potential mechanisms of atherogenesis. In addition, the use of cDNA microarrays may prove useful for the study of host cell responses to C, pneumoniae infection during latent and replicative stages of infectio n and related pathology.