Tumor necrosis factor modulates fibroblast apoptosis, PMN recruitment, and osteoclast formation in response to P. gingivalis infection.
P. gingivalis is an important oral pathogen, which has been closely linked to periodontal disease as well as lesions of endodontic origin. Both infections are associated with a decrease in fibroblast numbers, formation of an inflammatory infiltrate, and bone resorption. The goal of this study was to investigate the role that the host response plays in the capacity of P. gingivalis to stimulate fibroblast apoptosis, PMN recruitment, and osteoclastogenesis. This was accomplished by the use of an in vivo calvarial model in mice with targeted deletion of TNF receptors p55 and p75 and matched wild-type mice. The results indicate that P. gingivalis induces fibroblast apoptosis in vivo and establish for the first time that this involves the stimulation of a host response. Moreover, bacteria-stimulated PMN recruitment and osteoclastogenesis were also dependent upon the host response. The results suggest that much of the damage caused by P. gingivalis infection, including fibroblast apoptosis, at least under some circumstances, results from stimulation of the host response rather than the direct effect of bacterial products. Furthermore, this may represent a more general mechanism by which bacterial challenge induces apoptosis of matrix-producing cells through the induction of TNF.
Graves
D T
DT
Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, MA 02118, USA. dgraves@bu.edu
Oskoui
M
M
Volejnikova
S
S
Naguib
G
G
Cai
S
S
Desta
T
T
Kakouras
A
A
Jiang
Y
Y
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D016866:Bacteroidaceae Infections / Q000276:immunology / Q000503:physiopathology*; D001862:Bone Resorption / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000502:physiology*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D020556:Neutrophil Infiltration / Q000276:immunology / Q000502:physiology*; D010010:Osteoclasts / Q000502:physiology*; D010510:Periodontal Diseases / Q000382:microbiology / Q000503:physiopathology; D016966:Porphyromonas gingivalis / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology; D012886:Skull / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008565:Membrane Proteins; C097324:P55-L5 protein, Borrelia burgdorferi; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C075509:major surface protein, Porphyromonas gingivalis