The dual role of p55 tumour necrosis factor-α receptor inActinobacillus actinomycetemcomitans-induced experimental periodontitis: host protection and tissue destruction

Abstract

SummaryInflammatory 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)-a modulates the outcome of Actinobacillus actinomycetemcomitans-induced periodontal disease in mice. Our results showed that TNF-a receptor p55-deficient mice [p55TNF-knockout (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-a 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-a receptor p55, and its role in providing immune protection to A. actinomycetemcomitans periodontal infection.

TBX21-1993T/C (rs4794067) polymorphism is associated with increased risk of chronic periodontitis and increased T-bet expression in periodontal lesions, but does not significantly impact the IFN-g transcriptional level or the pattern of periodontophatic bacterial infection

“…Additionally, we must consider that other cytokines, such as TNF-a and IL-6, are supposed to contribute to the control of periodontal infection, as suggested by experimental models and human studies data. [33][34][35] It is also important to consider that the experimental evidence linking IFN-g with the control of periodontal infection derives from IFN-KO mice, which obviously represent an extreme situation that does not reflect the variation in IFN-g levels observed in humans. 13 Correspondingly, published evidence from our group demonstrated that after the hostś immune response reach a minimal threshold that confers protection, the increase of host responsiveness in degree/intensity does not provide additional protection and, conversely result in heightened tissue damage.…”

Proteína C-reactiva ultrasensible en pacientes con y sin periodontitis crónica severa generalizada

“…Además, las infecciones orales crónicas, en especial las que alcanzan los tejidos periodontales, vienen siendo indicadas como agentes que pueden contribuir al desencadenamiento de una respuesta inflamatoria sistémica debido a la relación existente entre las enfermedades periodontales y episodios inflamatorios (16)(17)(18)(19). Según Dasanayake (20) e Moutsopoulos (21), durante una infección periodontal, mediadores inflamatorios como la interleuquina-1 (IL-1), el factor de II).…”

Envolvimento de sinais coestimulatórios na periodontite apical crônica em humanos

“…A persistência da agressão bacteriana leva a constante liberação de IFN-γ pelo hospedeiro, contribuindo para a permanência do quadro inflamatório (GARLET et al, 2006). A IL-10 apresenta propriedades anti-inflamatórias reduzindo a expressão de moléculas coestimulatórias em células apresentadoras de antígenos e inibindo a síntese de citocinas inflamatórias e Th1 por células T, NK e macrófagos ROUSSET et al, 1992;MOORE et al, 1993;HAMILTON et al, 1999;PESTKA et al, 2004).…”

“…Esta citocina age em várias fases dos mecanismos de recrutamento do leucócito, induzindo o aumento de produção de moléculas de adesão e a produção de quimiocinas e metaloproteinases da matriz (MMP) (PFIZENMAIER; WAJANT; GRELL, 1996, DINARELLO, 2000. Além disso, TNF-α estimula a apresentação de antígenos, a expressão de moléculas coestimulatórias e a atividade bactericida dos fagócitos (GARLET et al, 2006).…”

“…Macrófagos podem ser estimulados por TNF-α a produzirem óxido nítrico, outra molécula implicada à reabsorção óssea (GARLET et al, 2006).…”