The essential role of toll like receptor‐4 in the control of <i>Aggregatibacter actinomycetemcomitans</i> infection in mice

Lima, Hayana Ramos; Gelani, Valéia; Fernandes, Ana Paula; Gasparoto, Thaís Helena; Torres, Sérgio Aparecido; Santos, Carlos; Garlet, Gustavo; Silva, João; Campanelli, Ana Paula

doi:10.1111/j.1600-051x.2009.01531.x

Cited by 41 publications

(44 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Each mandible was then processed for paraffin embedding, and 4-m-thick sections were obtained for each. The first section was stained with hematoxylin and eosin (H&E) for histological observations, while the next serial section was stained with tartrate-resistant acid phosphatase (TRAP) to reveal osteoclasts, which are considered to be TRAP-positive multinucleated cells (35)(36)(37). The number of osteoclasts on the interradicular septum (bone surface) (Oc.N/BS) was determined, and the osteoclast surface on the interradicular septum (bone surface) (Oc.S/BS) was evaluated, by scoring the TRAP-positive multinucleated cells attached to the bone surface as defined by Parfitt et al (38,39).…”

Section: Methodsmentioning

confidence: 99%

Inflammatory Bone Loss in Experimental Periodontitis Induced by Aggregatibacter actinomycetemcomitans in Interleukin-1 Receptor Antagonist Knockout Mice

et al. 2014

View full text Add to dashboard Cite

cThe interleukin-1 receptor antagonist (IL-1Ra) binds to IL-1 receptors and inhibits IL-1 activity. However, it is not clear whether IL-1Ra plays a protective role in periodontal disease. This study was undertaken to compare experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in IL-1Ra knockout (KO) mice and wild-type (WT) mice. Computed tomography (CT) analysis and hematoxylin-and-eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining were performed. In addition, osteoblasts were isolated; the mRNA expression of relevant genes was assessed by real-time quantitative PCR (qPCR); and calcification was detected by Alizarin Red staining. Infected IL-1Ra KO mice exhibited elevated (P, <0.05) levels of antibody against A. actinomycetemcomitans, bone loss in furcation areas, and alveolar fenestrations. Moreover, protein for tumor necrosis factor alpha (TNF-␣) and IL-6, mRNA for macrophage colony-stimulating factor (M-CSF), and receptor activator of NF-B ligand (RANKL) in IL-1Ra KO mouse osteoblasts stimulated with A. actinomycetemcomitans were increased (P, <0.05) compared to in WT mice. Alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN)/bone gla protein (BGP), and runt-related gene 2 (Runx2) mRNA levels were decreased (P, <0.05). IL-1␣ mRNA expression was increased, and calcification was not observed, in IL-1 Ra KO mouse osteoblasts. In brief, IL-1Ra deficiency promoted the expression of inflammatory cytokines beyond IL-1 and altered the expression of genes involved in bone resorption in A. actinomycetemcomitans-infected osteoblasts. Alterations consistent with rapid bone loss in infected IL-Ra KO mice were also observed for genes expressed in bone formation and calcification. In short, these data suggest that IL-1Ra may serve as a potential therapeutic drug for periodontal disease.

show abstract

Section: Methodsmentioning

confidence: 99%

Inflammatory Bone Loss in Experimental Periodontitis Induced by Aggregatibacter actinomycetemcomitans in Interleukin-1 Receptor Antagonist Knockout Mice

et al. 2014

View full text Add to dashboard Cite

show abstract

“…After TLRs activation, an intracellular signaling cascade is initiated. This signalling cascade involves activation of transcription factors and the subsequent inflammatory cytokines expression, leukocyte migration and osteoclastogenesis (Lima et al, 2010, Nakamura et al, 2008. In accordance, the absence of TLR2 or TLR4 results in reduction of alveolar bone loss in mice after P. gingivalis infection (Costalonga et al, 2009, Lima et al, 2010, Nakamura et al, 2008.…”

Section: Classic Inflammatory Cytokines Role In Periodontal and Periamentioning

confidence: 67%

“…This signalling cascade involves activation of transcription factors and the subsequent inflammatory cytokines expression, leukocyte migration and osteoclastogenesis (Lima et al, 2010, Nakamura et al, 2008. In accordance, the absence of TLR2 or TLR4 results in reduction of alveolar bone loss in mice after P. gingivalis infection (Costalonga et al, 2009, Lima et al, 2010, Nakamura et al, 2008. Besides TLRs, the nucleotide-binding oligomerization domain (NOD) receptors and the inflammasome system have been described as potential accessory molecules in triggering innate host response against periodontal pathogens (Okugawa & Bostanci, 2009, Uehara & Takada, 2007.…”

Section: Classic Inflammatory Cytokines Role In Periodontal and Periamentioning

confidence: 90%

The Role of Chemokines and Cytokines in the Pathogenesis of Periodontal and Periapical Lesions: Current Concepts

Garlet¹,

Aranha²,

Silveira³

et al. 2012

Inflammation, Chronic Diseases and Cancer - Cell and Molecular Biology, Immunology and Clinical Bases

View full text Add to dashboard Cite

“…Other models include the localized injection of the pathogen or a bacterial component such as lipopolysaccharide into the palatal gingival tissue (15)(16)(17)(18)(19). Furthermore, periodontal disease in mice has been commonly induced by inoculating the pathogen with a microsyringe or micropipette or by oral gavage, respectively (20)(21)(22)(23)(24)(25)(26)(27)(28). However, the limitation of all experimental models used so far is that they are contrary to the natural route of…”

Section: Discussionmentioning

confidence: 99%

NADPH Oxidase Contributes to Resistance against Aggregatibacter actinomycetemcomitans-Induced Periodontitis in Mice

et al. 2017

View full text Add to dashboard Cite

Aggregatibacter actinomycetemcomitans is a Gram-negative commensal bacterium of the oral cavity which has been associated with the pathogenesis of periodontitis with severe alveolar bone destruction. The role of host factors such as reactive oxygen and nitrogen intermediates in periodontal A. actinomycetemcomitans infection and progression to periodontitis is still ill-defined. Therefore, this study aimed to analyze the role of NADPH oxidase and inducible nitric oxide synthase (iNOS) in a murine model of A. actinomycetemcomitans-induced periodontitis. NADPH oxidase-deficient (gp91 phox knockout [KO]), iNOS-deficient (iNOS KO), and C57BL/6 wild-type mice were orally infected with A. actinomycetemcomitans and analyzed for bacterial colonization at various time points. Alveolar bone mineral density and alveolar bone volume were quantified by three-dimensional microcomputed tomography, and the degree of tissue inflammation was calculated by histological analyses. At 5 weeks after infection, A. actinomycetemcomitans persisted at significantly higher levels in the murine oral cavities of infected gp91 phox KO mice than in those of iNOS KO and C57BL/6 mice. Concomitantly, alveolar bone mineral density was significantly lower in all three infected groups than in uninfected controls, but with the highest loss of bone density in infected gp91 phox KO mice. Only infected gp91 phox KO mice revealed significant loss of alveolar bone volume and enhanced inflammatory cell infiltration, as well as an increased number of osteoclasts. Our results indicate that NADPH oxidase is important to control A. actinomycetemcomitans infection in the murine oral cavity and to prevent subsequent alveolar bone destruction and osteoclastogenesis.

show abstract

The essential role of toll like receptor‐4 in the control of Aggregatibacter actinomycetemcomitans infection in mice

Abstract: The results of this study highlighted the role of TLR4 in controlling A. actinomycetemcomitans infection.

Cited by 41 publications

References 49 publications

Inflammatory Bone Loss in Experimental Periodontitis Induced by Aggregatibacter actinomycetemcomitans in Interleukin-1 Receptor Antagonist Knockout Mice

Inflammatory Bone Loss in Experimental Periodontitis Induced by Aggregatibacter actinomycetemcomitans in Interleukin-1 Receptor Antagonist Knockout Mice

The Role of Chemokines and Cytokines in the Pathogenesis of Periodontal and Periapical Lesions: Current Concepts

NADPH Oxidase Contributes to Resistance against Aggregatibacter actinomycetemcomitans-Induced Periodontitis in Mice

Contact Info

Product

Resources

About