The dual role of p55 tumour necrosis factor-alpha receptor in Actinobacillus actinomycetemcomitans-induced experimental periodontitis: host protection and tissue destruction.
Inflammatory immune reactions in response to periodontopathogens are thought to protect the host against infection, but may trigger periodontal destruction. Thus, we examined the mechanisms by which the proinflammatory cytokine tumour necrosis factor (TNF)-alpha modulates the outcome of Actinobacillus actinomycetemcomitans-induced periodontal disease in mice. Our results showed that TNF-alpha receptor p55-deficient mice [p55TNF-knock-out (KO)] developed a less severe periodontitis in response to A. actinomycetemcomitans infection, characterized by significantly less alveolar bone loss and inflammatory reaction. Real-time polymerase chain reaction (PCR) demonstrated that levels of chemokines (CXCL1, 3 and 10; CCL3 and 5) and their receptors (CXCR2 and 3, CCR5) were lower in p55TNF-KO mice, as were matrix metalloproteinase (MMP)-1, 2 and 9 and receptor activator of nuclear factor kB ligand (RANKL) mRNA levels. However, the absence of the TNF-alpha p55 results in an impairment of protective immunity to A. actinomycetemcomitans infection, characterized by increased bacterial load and higher levels of C-reactive protein during the course of disease. Such impaired host response may be the result of the reduced chemoattraction of lymphocytes, neutrophils and macrophages, and reduced inducible nitric oxide synthase expression (iNOS) and myeloperoxidase (MPO) production in periodontal tissues of p55 TNF-KO mice. Our results demonstrate the mechanisms involved determining periodontal disease severity by TNF-alpha receptor p55, and its role in providing immune protection to A. actinomycetemcomitans periodontal infection.
Garlet
G P
GP
Department of Biological Sciences, School of Dentistry of Bauru, Bauru, Brazil. garletgp@usp.br
Cardoso
C R B
CR
Campanelli
A P
AP
Ferreira
B R
BR
Avila-Campos
M J
MJ
Cunha
F Q
FQ
Silva
J S
JS
D000189:Actinobacillus Infections / Q000276:immunology* / Q000473:pathology; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology; D016301:Alveolar Bone Loss; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D019742:Chemokines, CC / Q000032:analysis / Q000235:genetics; D019743:Chemokines, CXC / Q000032:analysis / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D053583:Interleukin-1beta / Q000032:analysis / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010518:Periodontitis / Q000276:immunology* / Q000473:pathology; D010519:Periodontium / Q000276:immunology* / Q000473:pathology; D009195:Peroxidase / Q000032:analysis; D053245:RANK Ligand / Q000032:analysis / Q000235:genetics; D019713:Receptors, CCR5 / Q000032:analysis / Q000235:genetics; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis / Q000235:genetics; D023063:Receptors, Interleukin-8B / Q000032:analysis / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053319:Tumor Necrosis Factor Decoy Receptors / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000907:Antibodies, Bacterial; C515187:CXCR3 protein, human; C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D019742:Chemokines, CC; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; C515188:Cxcr3 protein, mouse; D017931:DNA Primers; D053583:Interleukin-1beta; D053245:RANK Ligand; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D023063:Receptors, Interleukin-8B; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C069521:recombinant human tumor necrosis factor-binding protein-1; D007371:Interferon-gamma; D002097:C-Reactive Protein; D009195:Peroxidase; D020782:Matrix Metalloproteinases