Differences in cell activation by Chlamydophila pneumoniae and Chlamydia trachomatis infection in human endothelial cells.
Seroepidemiological studies and demonstration of viable bacteria in atherosclerotic plaques have linked Chlamydophila pneumoniae infection to the development of chronic vascular lesions and coronary heart disease. In this study, we characterized C. pneumoniae-mediated effects on human endothelial cells and demonstrated enhanced phosphorylation and activation of the endothelial mitogen-activated protein kinase (MAPK) family members extracellular receptor kinase (ERK1/2), p38-MAPK, and c-Jun-NH2 kinase (JNK). Subsequent interleukin-8 (IL-8) expression was dependent on p38-MAPK and ERK1/2 activation as demonstrated by preincubation of endothelial cells with specific inhibitors for the p38-MAPK (SB202190) or ERK (U0126) pathway. Inhibition of either MAPK had almost no effect on intercellular cell adhesion molecule 1 (ICAM-1) expression. While Chlamydia trachomatis was also able to infect endothelial cells, it did not induce the expression of endothelial IL-8 or ICAM-1. These effects were specific for a direct stimulation with viable C. pneumoniae and independent of paracrine release of endothelial cell-derived mediators like platelet-activating factor, NO, prostaglandins, or leukotrienes. Thus, C. pneumoniae triggers an early signal transduction cascade in target cells that could lead to endothelial cell activation, inflammation, and thrombosis, which in turn may result in or promote atherosclerosis.
Krüll
M
M
Department of Internal Medicine/Infectious Diseases, Charité, University Medicine Berlin, Augustenburger Platz 1, 13353, Germany. matthias.kruell@charite.de
Kramp
J
J
Petrov
T
T
Klucken
A C
AC
Hocke
A C
AC
Walter
C
C
Schmeck
B
B
Seybold
J
J
Maass
M
M
Ludwig
S
S
Kuipers
Jens G
JG
Suttorp
N
N
Hippenstiel
S
S
D002692:Chlamydia trachomatis / Q000472:pathogenicity*; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D042783:Endothelial Cells / Q000201:enzymology / Q000382:microbiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000382:microbiology*; D004789:Enzyme Activation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D014471:Umbilical Veins / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1; D048056:Mitogen-Activated Protein Kinase 9; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases