title: Lactoferrin knockout mice demonstrates greater susceptibility to Aggregatibacter actinomycetemcomitans-induced periodontal disease.
abstract: BACKGROUND
  Among the innate defense mechanisms in the oral cavity, lactoferrin (LF) is a vital antimicrobial that can modify the host response against periodontopathogens. Aggregatibacter actinomycetemcomitans is the main periodontopathogen of localized aggressive periodontitis. The aim of this study is to evaluate the role of LF during A. actinomycetemcomitans-induced periodontitis.
  
  
  METHODS
  Differences in the expression levels of cytokines, chemokines, chemokine receptors, and bone loss markers between wild-type (WT) and LF knockout mice (LFKO(-/-)) were evaluated by real time-PCR. Serum IgG and LF levels were quantified by ELISA. Alveolar bone loss among the groups was estimated by measuring the distance from cemento-enamel junction (CEJ) to the alveolar bone crest (ABC) at 20 molar sites.
  
  
  RESULTS
  Oral infection with A. actinomycetemcomitans increased LF levels in periodontal tissue (P = 0.01) and saliva (P = 0.0004) of wild-type infected (WTI) mice compared to wild-type control mice. Pro-inflammatory cytokines such as interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-12 were increased in the infected LF knockout (LFKO(-/-)I) mice compared to the WTI mice, whereas the anti-inflammatory cytokines IL-4 and IL-10 were decreased. Chemokines and chemokine receptors showed different expression patterns between WTI and LFKO(-/-)I mice. The LFKO(-/-)I mice developed increased bone loss (P = 0.002), in conjunction with increased expression of receptor activator of nuclear factor-κB ligand and decrease in osteoprotegerin, compared to WTI mice.
  
  
  CONCLUSIONS
  These results demonstrate that the infected LFKO(-/-) mice were more susceptible to A. actinomycetemcomitans-induced alveolar bone loss, with different patterns of immune responses compared to those of WTI mice.
authors: Department of Oral Biology, Rutgers School of Dental Medicine, Newark, NJ.
authors: S K
authors: SK
authors: Velusamy
authors: K
authors: K
authors: Ganeshnarayan
authors: K
authors: K
authors: Markowitz
authors: H
authors: H
authors: Schreiner
authors: D
authors: D
authors: Furgang
authors: D H
authors: DH
authors: Fine
authors: K
authors: K
authors: Velliyagounder
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D010520:Aggressive Periodontitis / Q000276:immunology / Q000382:microbiology*; D016301:Alveolar Bone Loss / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D000818:Animals; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007378:Interleukins / Q000032:analysis; D007781:Lactoferrin / Q000097:blood / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D053244:Osteoprotegerin / Q000032:analysis; D016871:Pasteurellaceae Infections / Q000276:immunology / Q000382:microbiology; D010519:Periodontium / Q000276:immunology / Q000382:microbiology; D053245:RANK Ligand / Q000032:analysis; D019707:Receptors, Chemokine / Q000276:immunology; D012463:Saliva / Q000737:chemistry; D019237:Tooth Cervix / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D033921:Vesicular Transport Proteins
chemical_list: D018925:Chemokines; D016207:Cytokines; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D015850:Interleukin-6; D007378:Interleukins; D053244:Osteoprotegerin; D053245:RANK Ligand; D019707:Receptors, Chemokine; C545985:TXLNA protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D033921:Vesicular Transport Proteins; C577686:interleukin-6, mouse; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D007781:Lactoferrin