Published online before print January 13, 2005, doi: 10.1161/01.RES.0000155721.83594.2c
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Submitted on August 10, 2004
Revised on December 27, 2004
Accepted on January 3, 2005
Nod1-Mediated Endothelial Cell Activation by Chlamydophila Pneumoniae
Bastian Opitz ;
From the Department of Internal Medicine/Infectious Diseases (B.O., S.F., A.C.H., B.S., S.H., N.S., M.K.), Charité University Medicine Berlin, Berlin; and the Institute of Medical Microbiology and Hygiene (M.M.), University of Lübeck, Lübeck, Germany.
* To whom correspondence should be addressed. E-mail: matthias.kruell{at}charite.de.
Seroepidemiological and animal studies, as well as demonstration of viable bacteria in atherosclerotic plaques, have linked Chlamydophila pneumoniae infection to development of chronic vascular lesions and coronary heart disease. Inflammation and immune responses are dependent on host recognition of invading pathogens. The recently identified cytosolic Nod proteins are candidates for intracellular recognition of bacteria, such as the obligate intracellular chlamydia. In the present study, mechanisms of endothelial cell activation by C. pneumoniae via Nod proteins were examined. Viable, but not heat-inactivated, chlamydia activated human endothelial cells, suggesting that invasion of these cells is necessary for their profound activation. Endothelial cells express Nod1. Nod1 gene silencing by small interfering RNA reduced C pneumoniae-induced IL-8 release markedly. Moreover, in HEK293 cells, overexpressed Nod1 or Nod2 amplified the capacity of C pneumoniae to induce nuclear factor 
B (NF-B) activation. Interestingly, heat-inactivated bacteria were still able to induced a NF-B reporter gene activity via Nod proteins when transfected intracellularly, but not when provided from the extracellular side. In contrast, TLR2 sensed extracellular heat-inactivated chlamydia. In conclusion, we demonstrated that C pneumoniae induced a Nod1-mediated and Nod2-mediated NF-B activation in HEK293 cells. In endothelial cells, Nod1 played a dominant role in triggering a chlamydia-mediated inflammatory process.
Key words: endothelial cells • Nod proteins • Toll-like receptors • chlamydia • siRNA
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