title: Experimental periodontitis in mice selected for maximal or minimal inflammatory reactions: increased inflammatory immune responsiveness drives increased alveolar bone loss without enhancing the control of periodontal infection.
abstract: OBJECTIVE
  Inflammatory immune reactions that occur in response to periodontopathogens are thought to protect the host against infection, but may trigger periodontal destruction. However, the molecular and genetic mechanisms underlying host susceptibility to periodontal infection and to periodontitis development have still not been established in detail.
  
  
  METHODS
  In this study, we examined the mechanisms that modulate the outcome of Aggregatibacter (Actinobacillus) actinomycetemcomitans-induced periodontal disease in mice mouse strains selected for maximal (AIRmax) or minimal (AIRmin) inflammatory reactions.
  
  
  RESULTS
  Our results showed that AIRmax mice developed a more severe periodontitis than AIRmin mice in response to A. actinomycetemcomitans infection, and this periodontitis was characterized by increased alveolar bone loss and inflammatory cell migration to periodontal tissues. In addition, enzyme-linked immunosorbent assays demonstrated that the levels of the cytokines interleukin-1beta, tumor necrosis factor-alpha and interleukin-17 were higher in AIRmax mice, as were the levels of matrix metalloproteinase (MMP)-2, MMP-13 and receptor activator of nuclear factor-kappaB ligand (RANKL) mRNA levels. However, the more intense inflammatory immune reaction raised by the AIRmax strain, in spite of the higher levels of antimicrobial mediators myeloperoxidase and inducible nitric oxide synthase, did not enhance the protective immunity to A. actinomycetemcomitans infection, because both AIRmax and AIRmin strains presented similar bacterial loads in periodontal tissues. In addition, the AIRmax strain presented a trend towards higher levels of serum C-reactive protein during the course of disease.
  
  
  CONCLUSIONS
  Our results demonstrate that the intensity of the inflammatory immune reaction is associated with the severity of experimental periodontitis, but not with the control of A. actinomycetemcomitans periodontal infection, suggesting that the occurrence of hyperinflammatory genotypes may not be an evolutionary advantage in the complex host-pathogen interaction observed in periodontal diseases.
authors.affiliation: Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, FMRP/USP, SP, Brazil.
authors.forename: A P F
authors.initials: AP
authors.lastname: Trombone
authors.forename: S B
authors.initials: SB
authors.lastname: Ferreira
authors.forename: F M
authors.initials: FM
authors.lastname: Raimundo
authors.forename: K C R
authors.initials: KC
authors.lastname: de Moura
authors.forename: M J
authors.initials: MJ
authors.lastname: Avila-Campos
authors.forename: J S
authors.initials: JS
authors.lastname: Silva
authors.forename: A P
authors.initials: AP
authors.lastname: Campanelli
authors.forename: M
authors.initials: M
authors.lastname: De Franco
authors.forename: G P
authors.initials: GP
authors.lastname: Garlet
mesh_terms: D000189:Actinobacillus Infections / Q000276:immunology*; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D016301:Alveolar Bone Loss / Q000276:immunology* / Q000382:microbiology; D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis; D002465:Cell Movement / Q000502:physiology; D015169:Colony Count, Microbial; D004198:Disease Susceptibility / Q000276:immunology; D054884:Host-Pathogen Interactions; D020381:Interleukin-17 / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000032:analysis; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D053244:Osteoprotegerin / Q000032:analysis; D010518:Periodontitis / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D009195:Peroxidase / Q000032:analysis; D053245:RANK Ligand / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D053244:Osteoprotegerin; D053245:RANK Ligand; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; C506031:Tnfrsf11b protein, mouse; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse