Polymorphic membrane protein (PMP) 20 and PMP 21 of Chlamydia pneumoniae induce proinflammatory mediators in human endothelial cells in vitro by activation of the nuclear factor-kappaB pathway.
We tested whether polymorphic membrane proteins (PMPs) of Chlamydia pneumoniae might play a role in triggering an inflammatory response in human endothelial cells. Of 15 purified, recombinant chlamydial PMPs tested, 2 (PMP 20 and PMP 21) dose-dependently increased the production of the inflammatory mediators interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1), in cultured human endothelial cells; production of IL-8 was also increased. When endothelial cells were infected by live C. pneumoniae, an increase in the production of IL-6, IL-8, and MCP-1 was seen. We used adenovirus-induced overexpression of IkappaBalpha-an inhibitor of nuclear factor (NF)-kappaB-to demonstrate that PMP 20 and PMP 21 increase the production of IL-6 and MCP-1 in human endothelial cells by activation of the NF-kappaB pathway, because, in cells overexpressing IkappaBalpha, treatment with the respective PMP did not result in increased production of IL-6 and MCP-1. Thus, C. pneumoniae could, by interactions of its PMPs with the endothelium, contribute to the process of vascular injury during the development and progression of atherosclerotic lesions.
Niessner
Alexander
A
Department of Internal Medicine II, University of Vienna, Vienna, Austria.
Kaun
Christoph
C
Zorn
Gerlinde
G
Speidl
Walter
W
Türel
Zeynep
Z
Christiansen
Gunna
G
Pedersen
Anna-Sofie
AS
Birkelund
Svend
S
Simon
Susan
S
Georgopoulos
Apostolos
A
Graninger
Wolfgang
W
de Martin
Rainer
R
Lipp
Joachim
J
Binder
Bernd R
BR
Maurer
Gerald
G
Huber
Kurt
K
Wojta
Johann
J
D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D016993:Chlamydophila pneumoniae / Q000737:chemistry*; D016207:Cytokines / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology
D001425:Bacterial Outer Membrane Proteins; D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B