Porphyromonas gingivalis strain-dependent activation of human endothelial cells.
Porphyromonas gingivalis is an important bacterium involved in periodontal diseases. Colonization by periodontopathogens has been associated with severe local inflammatory reactions in the connective tissue. In this study we characterized P. gingivalis-mediated infection and activation of human umbilical vein endothelial cells by using two strains of different virulence capacities, strains ATCC 53977 and DSMZ 20709. Both strains were able to adhere to and infect endothelial cells with an infection rate of 0.48% for ATCC 53977 and 0.007% for DSMZ 20709. The triggering of two signal transduction pathways in P. gingivalis-infected endothelial cells was demonstrated for both strains, with a rapid increase of p38 mitogen-activated protein kinase phosphorylation and a more delayed degradation of IkappaBalpha, followed by nuclear translocation of NF-kappaB. In addition, both strains induced enhanced expression of endothelial adhesion molecules E-selectin and intracellular adhesion molecule 1 (ICAM-1). Target cell activation was independent of bacterial fimbriae expression since the fimA knockout strain A7436 DeltafimA induced the same level of ICAM-1 as the corresponding wild type (A7436-WT). Thus, two P. gingivalis strains, ATCC 53799 and DSMZ 20709, infect endothelial cells and trigger signaling cascades leading to endothelial activation, which in turn may result in or promote severe local and systemic inflammation.
Walter
Clemens
C
Department of Infectious Diseases, Charité, Berlin, Germany.
Zahlten
Janine
J
Schmeck
Bernd
B
Schaudinn
Christoph
C
Hippenstiel
Stefan
S
Frisch
Eckehard
E
Hocke
Andreas C
AC
Pischon
Nicole
N
Kuramitsu
Howard K
HK
Bernimoulin
Jean-Pierre
JP
Suttorp
Norbert
N
Krüll
Matthias
M
D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D036781:Fimbriae Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D016966:Porphyromonas gingivalis / Q000145:classification* / Q000502:physiology*; D015398:Signal Transduction; D013045:Species Specificity; D014471:Umbilical Veins / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases
D019040:E-Selectin; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C063055:fimbrillin; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D036781:Fimbriae Proteins; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases